Microfluidics: A New Tool for Modeling Cancer–Immune Interactions
Open accessAbstract
In recognition of the enormous potential of immunotherapies against cancer, research into the interactions between tumor and immune cells has accelerated, leading to the recent FDA approval of several drugs that reduce cancer progression. Numerous cellular and molecular interactions have been identified by which immune cells can intervene in the metastatic cascade, leading to the development of several in vivo and in vitro model systems that can recapitulate these processes. Among these, microfluidic technologies hold many advantages in terms of their unique ability to capture the essential features of multiple cell type interactions in three-dimensions while allowing tight control of the microenvironment and real-time monitoring. Here, we review current assays and discuss the development of new microfluidic technologies for immunotherapy.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
35 of 64 cited sources checked · 20 supported · 0 flagged · accuracy not yet measured
- Premisecitation
Cancer cells promoted macrophage proliferation in a microfluidic device.
“Furthermore, cancer cells promoted macrophage proliferation[64].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [64] source
The Results (Cell morphological observations; page unavailable) show a macrophage migrating toward bladder cancer cells in the microfluidic device, and the Results (Arg-1 expression in macrophages; page unavailable) report increased Arg-1 expression. Neither passage establishes that cancer cells promoted macrophage proliferation; migration and activation are different outcomes. (LLM, conf=0.85)
Experimental — accuracy not yet measured
- Premisecitation
Immunotherapies have shown promising results for reducing metastasis in melanoma or kidney cancer patients.
“Recently, immunotherapies have shown promising results for reducing metastasis in melanoma or kidney cancer patients[1, 2].”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [1] source
- cites [2] source
In “Evidence of clinical activity for PD1 blockade” (page unavailable), the review describes promising tumour regressions and clinical responses in patients with melanoma and renal cancer, including patients with metastatic tumours. It does not establish that immunotherapy reduced the occurrence or spread of metastases, as distinct from treating existing cancer. (LLM, conf=0.82)
Experimental — accuracy not yet measured
- Premisecitation
Macrophages in co-culture expressed more Arginine-1, analogous to macrophage activation in the tumor microenvironment.
“They also showed that macrophages in co-culture expressed more Arginine-1, in an analogous manner to macrophage activation in the tumor microenvironment.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [48] source
The Abstract and Results (‘Making up the experiment for data-drive’; page unavailable) describe co-culturing melanoma cells with mouse splenocytes and analyzing cell migration. Searches for Arginine-1, macrophage expression, and activation found no passage reporting increased Arginine-1 in co-cultured macrophages or comparing that response with activation in the tumor microenvironment. (LLM, conf=0.70)
Experimental — accuracy not yet measured
- Premisecitation
Immune cells can attenuate metastasis.
“On one hand, there is evidence that immune cells have the capability to attenuate metastasis[54–59], which provides insight into how to restore or enhance their ability to combat cancer.”
Quote in the paperSubstantial claim4 of 6 sources checked - Premisecitation
Cancer cells communicate with their microenvironment, specifically with organ-specific cells, resulting in organ-selectivity in metastasis.
“This is particularly important as there is growing evidence that cancer cells communicate with their microenvironment[29], specifically with organ-specific cells[30], resulting in organ-selectivity in metastasis[31].”
Quote in the paperSubstantial claim2 of 3 sources checked- cites [29] source
- cites [30] source
The Introduction (page unavailable) invokes the seed-and-soil hypothesis to explain why tumors metastasize to particular organs. The Discussion (page unavailable) supports a narrower finding: breast cancer cells alter the brain microenvironment, which contributes to metastatic progression. The paper does not establish that communication with organ-specific cells causes organ selectivity across metastases. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [31] source
- Premisecitation
Dormancy can be induced by endothelial-derived factors.
“Studies have shown that dormancy can be induced by endothelial derived factors[24], thus demonstrating the need for microfluidic models that recapitulate interactions between ECs and tumor cells, using for example µVNs.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [24] source
- Premisecitation
A major current limitation of in vitro metastatic models is their lack of organ-specificity.
“One of the major current limitations of in vitro metastatic models is their lack of organ-specificity[28].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [28] source
- Premisecitation
Recent studies increasingly use microvascular networks whose permeability, architecture and diameters are more similar to in vivo microvascular beds.
“Recent studies are increasingly employing microvascular networks (µVNs)[21, 23, 24], where the permeability, architecture and diameters of vessels are more similar to those found in in vivo microvascular beds (Figure 2A) [21].”
Quote in the paperSubstantial claim3 of 3 sources checked- cites [21] source
The Introduction describes recent development of perfusable 3D microvascular networks with a more physiologically relevant configuration, and the Discussion says their permeability is comparable to that of in vivo venules. The Results describe self-organized vessels with 8–96 μm lumens, but our copy does not compare those diameters with in vivo microvascular beds. (LLM, conf=0.83)
Experimental — accuracy not yet measured - cites [23] source
The Discussion (page not specified in our copy) describes a branched, lumenized vessel network whose heterogeneous diameters and morphology resemble tumor vasculature in vivo. This supports the architectural comparison, but the paper does not establish that the network’s permeability or vessel diameters are more similar to those of in vivo microvascular beds. (LLM, conf=0.85)
Experimental — accuracy not yet measured - cites [24] source
The Results section reports that the authors grew robust three-dimensional microvascular networks, supporting this paper as an example of a study using such networks. Our copy does not establish that their vessels’ permeability, architecture, or diameters are more similar to in vivo microvascular beds, nor does it document an increasing trend in their use. No page number is available in the indexed passages. (LLM, conf=0.84)
Experimental — accuracy not yet measured
- Premisecitation
Microfluidic assays have been designed to replicate aspects of several metastatic steps, including EMT, cancer cell invasion and adhesion, and intra- and extravasation.
“Microfluidic assays have been designed to replicate certain aspects of several of these steps, such as EMT[13, 14], cancer cell invasion and adhesion[15–17], and intra-[18, 19] and extravasation[17, 20– 22] (see Text Box 3).”
Quote in the paperSubstantial claim3 of 7 sources checked- cites [13] source
- cites [14] source
- cites [15] source
The Discussion describes a microfluidic system that models circulating breast cancer cells adhering to vascular endothelium under flow, supporting the adhesion part of the citation. It does not describe an assay that models cancer-cell invasion or extravasation. EMT and intravasation are attached to other citations in the citing sentence. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [16] source
- cites [17] source
- cites [18] sourceExperimental — accuracy not yet measured
- cites [19] sourceExperimental — accuracy not yet measured
- Premisecitation
Immune-deficient IRF-8 knockout mice develop more tumors with less immune cell infiltration than wild-type animals.
“These studies first showed that immune-deficient interferon regulatory factor-8 (IRF-8) knockout mice develop more tumors with less immune cell infiltration than wild type animals[50], and subsequently used a microfluidic assay to investigate the underlying mechanism in greater detail.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [50] source
The melanoma-growth section reports faster tumor growth and more lung metastatic foci in IRF-8 knockout mice, but does not establish that they developed more primary tumors. The immune-cell infiltration section reports fewer infiltrating T cells and dendritic cells in knockout tumors, while myeloid-derived suppressor cell infiltration was higher; the unqualified claim of less immune-cell infiltration misses that exception. (LLM, conf=0.85)
Experimental — accuracy not yet measured
- Interpretationcitation
Only a limited number of recent studies have employed microfluidics to investigate immune-cancer cell interactions.
“To the best of our knowledge, only a limited number of recent studies have employed microfluidics to investigate immune-cancer cell interactions[18, 48–52], possibly because microfluidic models are not yet widely available to cancer researchers.”
Quote in the paperSubstantial claim4 of 6 sources checked - Premisecitation
Immune cells can be pro-metastatic at different stages of cancer progression.
“On the other hand, it has been shown that immune cells can also be pro-metastatic at different stages of cancer progression (reviewed by Kitamura et al[37]).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [37] source
- Premisecitation
A macrophage cell line seeded in a 3D collagen gel in a microfluidic device assisted and increased intravasation of breast cancer cells through an endothelial monolayer, as observed in vivo.
“In another recent study, a macrophage cell line (RAW 264.7) seeded in a 3D collagen gel in a microfluidic device was shown to assist and increase the intravasation of breast cancer cells through an endothelial monolayer[18], as has been observed in vivo[63].”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [18] source
Materials and Methods identifies RAW264.7 as the macrophage cell line, and the Results report that macrophages increased breast cancer cell intravasation across the endothelial monolayer ninefold in the 3D microfluidic assay. The Results say the breast carcinoma cells were seeded in the 3D matrix, but do not establish that the macrophages were seeded in the collagen gel. The separate in-vivo comparison is attributed to citation [63], not this source. (LLM, conf=0.85)
Experimental — accuracy not yet measured - cites [63]
- Interpretationcitation
Challenges remain before microfluidic assays can be routinely used in the clinic.
“Yet, challenges remain before microfluidic assays can be routinely used in the clinic [82, 83] (Outstanding Question Box) [84].”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [82] source
- cites [83] source
The ‘Microfluidics and 3D cell culture: from exploration to validation to implementation’ section says microfluidic 3D culture models still need validation and describes diagnostic tests and personalized medicine as future applications. This supports the existence of barriers to clinical use, but the paper discusses 3D culture models specifically, not routine clinical use of microfluidic assays generally. The supplied copy does not give a page number for these passages. (LLM, conf=0.83)
Experimental — accuracy not yet measured - cites [84] source
- Premisecitation
The role of immune cells in cancer progression, such as macrophages, may differ between organs.
“We propose that cancer-immune cell interactions should be studied in organ-specific microfluidic models, since recent studies suggest that the role of immune cells in cancer progression, such as macrophages, may differ between organs[87].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [87] source
- Interpretationreasoning
Microfluidic platforms require only minute amounts of cells and reagents.
“Since these platforms are small, they require only minute amounts of cells and reagents that are often expensive, rare or difficult to obtain.”
Quote in the paperSubstantial claim - Premisereasoning
In vitro systems, including microfluidic platforms, have an advantage over animal studies for studying cancer-immune cell interactions because they can use multiple human cell types while animal studies contain non-human host cells.
“In vitro systems, including microfluidic platforms, present an important advantage over animal studies with regard to studying cancer-immune cell interactions.”
- Also stated in: § Microfluidic vs. traditional models for cancer and metastasis research · plain
“Namely, in vitro studies can be performed using multiple cell types - immune, cancer and stromal cells - that are exclusively of human origin, while animal studies will inherently contain non-human host cells.”
Quote in the paperSubstantial claim - Also stated in: § Microfluidic vs. traditional models for cancer and metastasis research · plain
- Interpretationcitation
The ability to establish precise gradients in microfluidic devices makes them useful for studying immune cell responses in vitro.
“It is the ability to establish such precise gradients in microfluidic devices that makes them useful for studying immune cell responses in vitro[44].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [44] source
- Interpretationreasoning
Microfluidics are most likely the best-suited in vitro systems for mimicking organ-specific environments because they permit precise control over the spatial distribution of different cell types.
“At the moment, microfluidics are most likely the best-suited in vitro systems for mimicking organ-specific environments because they permit precise control over the spatial distribution of different cell types that mimic the in vivo settings (see Text Box 2).”
Quote in the paperSubstantial claim - Premisecitation
A loss-of-function mutation in Fpr1 correlated with poor survival in breast and colorectal cancer patients receiving adjuvant chemotherapy.
“Recently, Vacchelli et al. identified a loss of-function mutation in the allele of the gene coding for formyl peptide receptor 1 (Fpr1) that correlated with poor survival in breast and colorectal cancer patients receiving adjuvant chemotherapy[62].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [62] source
- Interpretationreasoning
Microfluidic devices allow easier high-resolution imaging of all cells compared with larger traditional 3D in vitro models.
“More importantly, the distance from the biological samples in the device to the microscope objective is short and, therefore, it is easier to image all cells at high resolution, as opposed to imaging larger traditional 3D in vitro models.”
Quote in the paperSubstantial claim - Interpretationreasoning
Microfluidic assays improve physiological relevance over other in vitro models by allowing precise control of the cellular, physical and biochemical microenvironment.
“Overall, microfluidic assays represent a dramatic improvement in physiological relevance over other in vitro models because they allow for precise control of the cellular, physical and biochemical microenvironment”
Quote in the paperSubstantial claim - Interpretationreasoning
Low cell numbers in microfluidic devices can hinder downstream biochemical studies or quantification of secreted proteins.
“The low cell number can also be a drawback if a large number of cells is need for downstream biochemical studies (e.g., by western blotting) or if secreted proteins need to be quantified (e.g., by ELISA).”
Quote in the paperNot a substantial claim - Interpretationreasoning
The endothelium is a crucial feature of the microenvironment to include in microfluidic models of metastasis.
“Thus, the endothelium is a crucial feature of the microenvironment to be included in microfluidic models of metastasis.”
Quote in the paperSubstantial claim - Premisecitation
Microfluidic channels can establish physical or chemical gradients more precisely and more sustainably than macro-scale in vitro systems.
“These channels can also be used to precisely establish physical (e.g., interstitial pressure) or chemical (e.g., cytokines) complex gradients in the microfluidic assay in a more precise and sustained manner than in macro-scale in vitro systems[5].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] source
- Interpretationreasoning
Microfluidic technologies are particularly relevant for studying the metastatic cascade because metastatic spread occurs through several steps that are often difficult to resolve in vivo.
“They are particularly relevant for studying the metastatic cascade, since metastatic spread occurs through several steps that are often difficult to resolve in vivo.”
Quote in the paperSubstantial claim - Premisecitation
Fpr1-deficient immune cells interacted much less with dying cancer cells treated with anthracyclines than immune cells expressing functional Fpr1.
“This confirmed that Fpr1 deficient immune cells interacted much less with dying cancer cells treated with anthracyclines than immune cells expressing functional Fpr1 (Fig. 3B), explaining why Fpr1 deficiency leads to defective anticancer immune response and less efficient chemotherapy.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [62] source
- Interpretationcitation
High-resolution time-lapse imaging facilitated in microfluidic models is an important advantage for analyzing immune cell dynamics in real time.
“Finally, immune cells are highly mobile and high resolution time-lapse imaging facilitated in microfluidic models is an important advantage for analyzing their dynamics in real-time[45].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [45] source
- Premisecitation
Many current microfluidic platforms depend heavily on high-resolution imaging and time-consuming image and data analysis.
“Although these devices have better potential for high throughput testing than animal studies, many current microfluidic platforms depend heavily on high resolution imaging and similarly time-consuming image and data analysis[45].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [45] source
- Interpretationcitation
Manufacturability and scalability are challenges for microfluidic systems in translational immunology, limited by the predominant use of PDMS for making devices.
“Other challenges associated with microfluidic systems for translational immunology are manufacturability and scalability[66], limited by, for example, the predominant use of PDMS for making devices[84].”
Quote in the paperNot a substantial claim0 of 2 sources checked - Interpretationnone given
Microfluidic models can recapitulate key features of the immune microenvironment, such as chemical gradients, vascular flow and trans-endothelial migration.
“These models have also the ability to recapitulate key features of the immune microenvironment, such as chemical gradients, vascular flow and trans-endothelial migration.”
Quote in the paperNot a substantial claim - Interpretationnone given
Microfluidic models have become valuable tools for studying the metastatic cascade.
“Microfluidic models have become valuable tools for studying the metastatic cascade.”
Quote in the paperSubstantial claim
- Borderline: one of the tests for a substantial claim is unclear. 1
- May combine two claims. 16
- Classified as probably not a substantial claim. 8
Borderline on S3 (load-bearing): unclear from the text. May combine two claims.
PremisecitationImmune spleen cells lacking IRF-8 do not migrate toward cancer cells or interact with them as efficiently as wild-type immune cells.
“Specifically, they showed that immune spleen cells lacking IRF-8 do not migrate towards cancer cells, nor interact with them as efficiently as wild type immune cells[48–50], suggesting a mechanism to explain why IRF-8 knock-out cells fail to exert proper immune-surveillance leading to a heavier metastatic burden.”
Quote in the paperNot a substantial claim2 of 3 sources checkedMay combine two claims.
PremisecitationImmune cells can be educated by cancer cells to become tolerant to tumors and even promote tumor growth and metastasis.
“Although it was first observed that immune cells play an anti-tumorigenic role, it was later realized they can be “educated” by cancer cells to become tolerant to tumors and even promote tumor growth and metastasis[37].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [37] source
May combine two claims.
InterpretationcitationMicrovascular networks are a dramatic improvement over previous 2D extravasation models such as Boyden Transwell-chambers because transwells do not allow dynamic high-resolution single-cell imaging and microvascular networks better replicate 3D vessel architecture and endothelial barrier function.
“These µVNs represent a dramatic improvement over previous 2D extravasation models such as Boyden Transwell-chambers that consist of ECs seeded onto a permeable membrane inserted in a well-plate, since transwells do not allow for dynamic high resolution single cell imaging due to the long distance of the insert from the objective.”
- Also stated in: § Microfluidic: modeling the metastatic cascade · plain
“In addition, µVNs replicate better the 3D vessel architecture and endothelial barrier function [21].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [21] source
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
- Also stated in: § Microfluidic: modeling the metastatic cascade · plain
May combine two claims.
PremisecitationIntravital imaging requires specialized expertise and equipment, and high image resolution is harder in some visceral organs because of their depth.
“While intravital imaging has proven extremely useful in the study of metastasis[6–7], it requires specialized expertise and equipment, and high image resolution is harder to attain in some visceral organs due to the depth of their location.”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [6] source
- cites [7] source
The Introduction discusses expertise needed for microscopic inspection of plant pathogens, not intravital imaging. Searches for intravital imaging, metastasis, and depth-related limits on imaging visceral organs found no passage addressing the claim; page numbers are unavailable in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationNeutrophils assist tumor cell extravasation following platelet aggregation around the tumor cell.
“For example, neutrophils are known to assist with tumor cell extravasation following platelet aggregation around the tumor cell[60, 61].”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [60] source
- cites [61] source
The Results section ('Platelet-Derived TGFβ1 is Necessary for Metastasis In Vivo') reports tumor cells associated with platelets in blood vessels and evidence that platelet-derived TGFβ1 aids extravasation. Neither that passage nor the Discussion passages identify neutrophils as assisting extravasation; a search for 'neutrophils' found no supporting passage. Page numbers are unavailable in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationPDMS can adsorb small hydrophobic molecules, which can be problematic for drug screening studies.
“PDMS can also adsorb small hydrophobic molecules[9], which can be problematic for drug screening studies.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [9] source
Classified as probably not a substantial claim.
PremisecitationThe interplay of several types of immune cells is critical for some steps of the metastatic cascade.
“Finally, future studies should analyze the role of several types of immune cells simultaneously, as their interplay has been shown to be critical for some steps of the metastatic cascade[60, 61].”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [60] source
- cites [61] source
The Introduction (page unavailable) describes platelets shielding tumor cells from natural-killer-cell lysis, and the Discussion reports that platelet–tumor-cell signaling promotes metastatic seeding. These passages support a role for cellular interactions in metastasis, but they do not establish that interplay among several types of immune cells is critical to steps of the metastatic cascade. (LLM, conf=0.78)
Experimental — accuracy not yet measured
May combine two claims.
InterpretationreasoningThe immune cell response is a spatially orchestrated process occurring in different tissues, and it can be captured in microfluidic models through spatial compartmentalization.
“The immune cell response is a spatially orchestrated process, occurring in a variety of different tissues (i.e. bone marrow, blood stream and target tissue), which can be captured in microfluidic models through spatial compartmentalization.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationnone givenSome metastatic events such as intravasation can be rare and difficult to image in vivo, but their rate can be more readily modulated in vitro.
“Furthermore, some events of the metastatic cascade (e.g. intravasation) can be rare and thus difficult to image in vivobut this rate of occurrence can be more readily modulated in vitro.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationConditioned media from macrophages and myofibroblasts increased cancer cell migration, while TNF-α produced by macrophages counteracted the migration-promoting effects of myofibroblasts.
“This study showed that CM from macrophage and myofibroblasts increased the migration of cancer cells. Interestingly, tumor necrosis factor- α (TNF-α) produced by macrophages counteracted the migration-promoting effects of myofibroblasts.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [51] source
May combine two claims.
InterpretationreasoningMicrofluidic channels permit precise control of flow, enabling study of biomechanical processes such as shear stress.
“Uniquely, the presence of microfluidic channels permits precise control of flow, allowing the study of many important biomechanical processes such as shear stress.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationRetrieving cells from microfluidic devices for later biochemical studies is possible but not straightforward.
“For example, retrieving cells from microfluidic devices for subsequent biochemical studies is possible but not straightforward [6].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [6] source
Probably not a substantial claim: may not pass S2 (checkable), S4 (based).
Interpretationnone givenMicrofluidic systems are particularly powerful tools for replicating the metastatic environment.
“We propose that microfluidics systems are particularly powerful tools to replicate the metastatic environment and should thus be exploited to study cancer-immune cell interactions.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationnone givenMany immune cells exist under flow conditions in the bloodstream, and these conditions can be recreated through precise control of flow in microfluidic systems.
“In addition, many immune cells exist under flow conditions in the bloodstream that can be uniquely recreated through precise control of flow in microfluidic systems.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationTumor cells cultured in 3D spheroids show decreased production of TAA and HLA class I, as also observed in vivo.
“Importantly, these studies demonstrated important differences between 2D and 3D, with tumor cells cultured in 3D spheroids showing a decreased production of TAA and HLA class I (as also observed in vivo)[47].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [47] source
Probably not a substantial claim: may not pass S3 (load-bearing).
Interpretationnone givenMicrofluidic systems offer potential for high-throughput, quantitative clinical analyses.
“Microfluidic systems offer the potential for high throughput, quantitative clinical analyses.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
Interpretationnone givenMicrofluidic systems are uniquely positioned to facilitate personalized medicine because they need few patient cells and can potentially provide rapid automated results.
“Microfluidic systems are uniquely positioned to facilitate the development of personalized medicine because of the small number of cells needed from the patient and the potential to obtain rapid and automated results.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningMicrofluidic models can help characterize immune-cancer cell interactions that are therapeutic targets and can help test the efficacy of novel immunotherapies.
“Microfluidic models can not only help characterize the immune-cancer cell interactions that have recently become interesting therapeutic targets, but also help in testing the efficacy of novel immunotherapies.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationCurrent lab-on-a-chip models require external equipment and much human intervention.
“Indeed, these current “lab-on-a-chip” models are intended to facilitate time-consuming bench-top procedures, but are, after all, still “chips-in-a-lab”[86] that require external equipment (e.g. pumps, microscope) and much human intervention.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [86] source
Probably not a substantial claim: may not pass S2 (checkable).
InterpretationreasoningMicrofluidic systems could represent an important intermediate step bridging current in vitro high-throughput screens and animal studies and human clinical trials.
“Eventually, microfluidic systems could represent an important intermediate step, bridging current in vitro high throughput screens and animal studies and human clinical trials.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
Interpretationnone givenTo date, microfluidic studies have not been widely exploited to study cancer/immune cell interactions.
“Despite their tremendous experimental potential, to date, microfluidic studies have not been widely exploited to study cancer/immune cell interactions.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S2 (checkable).
InterpretationreasoningAn opportunity exists to capitalize on microfluidic models' capability to recapitulate cancer-immune cell interactions as they occur in vivo, especially during metastatic spread.
“Thus, an opportunity exists to capitalize on the capability of microfluidic models to recapitulate interactions between cancer and immune cells as they occur in vivo, especially during metastatic spread.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationAn estimated 85% of microfluidic-related publications appear in engineering rather than clinical or biological journals, mostly as proof-of-principle studies.
“Sackmann et al. estimated that 85% of microfluidic related publications are published in engineering, as opposed to clinical or biological journals, mostly as proof-of-principle studies[84].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [84] source
The paper relies on this without support.
No in vitro system, including microfluidic ones, can reproduce every aspect of in vivo complexity.
“Finally, care should be taken in extrapolating results from any in vitro study, including microfluidic ones, since they can never fully replicate all aspects of in vivo complexity.”
Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989 · see citing works
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838 · cited 1× · see citing works
“Recently, immunotherapies have shown promising results for reducing metastasis in melanoma or kidney cancer patients[1, 2].”
BackgroundThe origins and the future of microfluidics
Whitesides, G. M. (2006) · Nature · doi:10.1038/nature05058 · Cited by 9,687 · cited 1× · see citing works
“Microfluidics is a rapidly expanding technology that relies on the use of small channels, ranging from tens to hundreds of micrometers in height or width for handling small fluid volumes[4].”
BackgroundMolecular Mechanisms of Stress-Responsive Changes in Collagen and Elastin Networks in Skin
Aziz, J., Shezali, H., Radzi, Z., Yahya, N. A., Abu Kassim, N. H., Czernuszka, J., & Rahman, M. T. (2016) · Skin Pharmacology and Physiology · doi:10.1159/000447017 · Cited by 7,323 · see citing works
Macrophage Diversity Enhances Tumor Progression and Metastasis
Qian, B., & Pollard, J. W. (2010) · Cell · doi:10.1016/j.cell.2010.03.014 · Cited by 5,178 · cited 1× · see citing works
“Second, drug-resistance related problems are also minimized, since immune cells are less likely to acquire drug resistance than cancer cells[39].”
BackgroundThe pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited
Fidler, I. J. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1098 · Cited by 4,686 · cited 1× · see citing works
“This is particularly important as there is growing evidence that cancer cells communicate with their microenvironment[29], specifically with organ-specific cells[30], resulting in organ-selectivity in metastasis[31].”
BackgroundReconstituting organ-level lung functions on a chip
Huh, D., Matthews, B. D., Mammoto, A., Montoya-Zavala, M., Hsin, H. Y., & Ingber, D. E. (2010) · Science · doi:10.1126/science.1188302 · Cited by 4,250 · cited 1× · see citing works
“, an airliquid interface for mimicking the pulmonary airways[34]).”
BackgroundDissemination and growth of cancer cells in metastatic sites
Chambers, A. F., Groom, A. C., & MacDonald, I. C. (2002) · Nature reviews. Cancer · doi:10.1038/nrc865 · Cited by 3,920 · cited 1× · see citing works
“These steps include an epithelial-to-mesenchymal transition (EMT), invasion, intravasation, transport of circulating tumor cells (CTCs) in the bloodstream, extravasation in the distant organ, and recolonization at the metastatic site[12] (Fig.”
BackgroundMicroenvironmental regulation of metastasis
Joyce, J. A., & Pollard, J. W. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2618 · Cited by 3,684 · cited 1× · see citing works
“This is particularly important as there is growing evidence that cancer cells communicate with their microenvironment[29], specifically with organ-specific cells[30], resulting in organ-selectivity in metastasis[31].”
BackgroundThe present and future role of microfluidics in biomedical research
Sackmann, E. K., Fulton, A. L., & Beebe, D. J. (2014) · Nature · doi:10.1038/nature13118 · Cited by 2,995 · cited 3× · see citing works
“estimated that 85% of microfluidic related publications are published in engineering, as opposed to clinical or biological journals, mostly as proof-of-principle studies[84].”
BackgroundMethodParadoxical roles of the immune system during cancer development
de Visser, K. E., Eichten, A., & Coussens, L. M. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1782 · Cited by 2,261 · cited 1× · see citing works
“There are, however, many animal studies that have revealed the paradoxical interactions of immune and cancer cells[53] during metastatic progression.”
ResultFrom 3D cell culture to organs-on-chips
Huh, D., Hamilton, G. A., & Ingber, D. E. (2011) · Trends in Cell Biology · doi:10.1016/j.tcb.2011.09.005 · Cited by 1,834 · see citing works
Labelle, M., Begum, S., & Hynes, R. O. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.09.009 · Cited by 1,833 · cited 2× · see citing works
“For example, neutrophils are known to assist with tumor cell extravasation following platelet aggregation around the tumor cell[60, 61].”
BackgroundKim, H. J., Huh, D., Hamilton, G., & Ingber, D. E. (2012) · Lab on a Chip · doi:10.1039/c2lc40074j · Cited by 1,734 · cited 1× · see citing works
“In addition, several “organ-on-achip” studies have developed microfluidic models for studying inflammation in the lung[74] or gut[75].”
Combining immunotherapy and targeted therapies in cancer treatment
Vanneman, M. W., & Dranoff, G. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3237 · Cited by 1,583 · cited 2× · see citing works
“Finally, treatment effects can be more sustained than with conventional regimens, due to immune memory[40].”
BackgroundImmune cell promotion of metastasis
Kitamura, T., Qian, B.-Z., & Pollard, J. W. (2015) · Nature Reviews Immunology · doi:10.1038/nri3789 · Cited by 1,158 · cited 3× · see citing works
“On the other hand, it has been shown that immune cells can also be pro-metastatic at different stages of cancer progression (reviewed by Kitamura et al[37]).”
BackgroundInfluentialThe perivascular niche regulates breast tumour dormancy
Ghajar, C. M., Peinado, H., Mori, H., Matei, I. R., Evason, K. J., Brazier, H., Almeida, D., Koller, A., Hajjar, K. A., Stainier, D. Y. R., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2767 · Cited by 1,148 · cited 3× · see citing works
“Recent studies are increasingly employing microvascular networks (μVNs)[21, 23, 24], where the permeability, architecture and diameters of vessels are more similar to those found in in vivo microvascular beds (Figure 2A) [21].”
BackgroundMacrophage Regulation of Tumor Responses to Anticancer Therapies
De Palma, M., & Lewis, C. E. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.02.013 · Cited by 1,079 · cited 1× · see citing works
“enhance or hinder) tumor responses to traditional anti-cancer therapies[41, 42].”
BackgroundDirect Visualization of Macrophage-Assisted Tumor Cell Intravasation in Mammary Tumors
Wyckoff, J. B., Wang, Y., Lin, E. Y., Li, J.-F., Goswami, S. K., Stanley, E. R., Segall, J. E., Pollard, J. W., & Condeelis, J. S. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-1823 · Cited by 1,053 · see citing works
Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function
Zervantonakis, I. K., Hughes-Alford, S. K., Charest, J. L., Condeelis, J. S., Gertler, F. B., & Kamm, R. D. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1210182109 · Cited by 872 · cited 3× · see citing works
“Microfluidic assays have been designed to replicate certain aspects of several of these steps, such as EMT[13, 14], cancer cell invasion and adhesion[15–17], and intra-[18, 19] and extravasation[17, 20– 22] (see Text Box 3).”
BackgroundMethodSelf-citationEngineering of functional, perfusable 3D microvascular networks on a chip
Kim, S., Lee, H., Chung, M., & Jeon, N. L. (2013) · Lab on a Chip · doi:10.1039/c3lc41320a · Cited by 872 · cited 1× · see citing works
“These μVNs arise from the self-organization of ECs suspended in a hydrogel in the presence of fibroblasts[25, 26] or mesenchymal stem cells[27].”
BackgroundTumor entrained neutrophils inhibit seeding in the premetastatic lung
Granot, Z., Henke, E., Comen, E. A., King, T. A., Norton, L., & Benezra, R. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.08.012 · Cited by 782 · see citing works
Isolation and retrieval of circulating tumor cells using centrifugal forces
Hou, H. W., Warkiani, M. E., Khoo, B. L., Li, Z., Soo, R. A., Tan, D. S.-W., Lim, W., Han, J., Bhagat, A. A. S., & Lim, C. T. (2013) · Scientific Reports · doi:10.1038/srep01259 · Cited by 737 · cited 3× · see citing works
“Eventually, different components could be integrated in one microfluidic chip for increased throughput and automation, e.g. isolation of CTCs followed by diagnostic tests in a single microfluidic set-up.”
BackgroundBiological implications of polydimethylsiloxane-based microfluidic cell culture
Regehr, K. J., Domenech, M., Koepsel, J. T., Carver, K. C., Ellison-Zelski, S. J., Murphy, W. L., Schuler, L. A., Alarid, E. T., & Beebe, D. J. (2009) · Lab on a Chip · doi:10.1039/b903043c · Cited by 719 · cited 1× · see citing works
“PDMS can also adsorb small hydrophobic molecules[9], which can be problematic for drug screening studies.”
BackgroundQian, B., Deng, Y., Im, J. H., Muschel, R. J., Zou, Y., Li, J., Lang, R. A., & Pollard, J. W. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006562 · Cited by 664 · see citing works
Chen, Q., Zhang, X. H.-F., & Massagué, J. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.08.025 · Cited by 619 · cited 1× · see citing works
“We propose that cancer-immune cell interactions should be studied in organ-specific microfluidic models, since recent studies suggest that the role of immune cells in cancer progression, such as macrophages, may differ between organs[87].”
BackgroundIlluminating the metastatic process
Sahai, E. A. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2229 · Cited by 566 · see citing works
Platelets guide the formation of early metastatic niches
Labelle, M., Begum, S., & Hynes, R. O. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1411082111 · Cited by 555 · cited 2× · see citing works
“For example, neutrophils are known to assist with tumor cell extravasation following platelet aggregation around the tumor cell[60, 61].”
BackgroundEngineered In Vitro Disease Models
Benam, K. H., Dauth, S., Hassell, B., Herland, A., Jain, A., Jang, K.-J., Karalis, K., Kim, H. J., MacQueen, L., Mahmoodian, R., et al. (2015) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012414-040418 · Cited by 554 · see citing works
A microfluidic 3D in vitro model for specificity of breast cancer metastasis to bone
Bersini, S., Jeon, J. S., Dubini, G., Arrigoni, C., Chung, S., Charest, J. L., Moretti, M., & Kamm, R. D. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2013.11.050 · Cited by 534 · cited 1× · see citing works
“To date, studies have added organ-specific cell types[32] or chemokines[17] to microfluidic models and replicated certain aspects of organ architecture[33] (e.”
BackgroundSelf-citationPerivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy
Hughes, R., Qian, B., Rowan, C., Muthana, M., Keklikoglou, I., Olson, O. C., Tazzyman, S. J., Danson, S. J., Addison, C., Clemons, M. J., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-3587 · Cited by 516 · cited 1× · see citing works
“enhance or hinder) tumor responses to traditional anti-cancer therapies[41, 42].”
BackgroundInterstitial flow influences direction of tumor cell migration through competing mechanisms
Polacheck, W. J., Charest, J. L., & Kamm, R. D. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1103581108 · Cited by 509 · see citing works
Self-citationLee, P. J., Hung, P. J., & Lee, L. P. (2007) · Biotechnology and Bioengineering · doi:10.1002/bit.21360 · Cited by 507 · see citing works
Eyles, J., Puaux, A.-L., Wang, X., Toh, B., Prakash, C., Hong, M., Tan, T. G., Zheng, L., Ong, L. C., Jin, Y., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci42002 · Cited by 506 · see citing works
Microfluidic 3D cell culture: from tools to tissue models
van Duinen, V., Trietsch, S. J., Joore, J., Vulto, P., & Hankemeier, T. (2015) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2015.05.002 · Cited by 500 · cited 2× · see citing works
“Results of microfluidic studies should be systematically validated by in vivo experiments[83] (see Outstanding questions).”
BackgroundMethodLabelle, M., & Hynes, R. O. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0329 · Cited by 488 · cited 1× · see citing works
“This is particularly relevant to the study of the immune system, which relies heavily on interactions between numerous cell types dispersed throughout the body (even during metastasis[85]).”
BackgroundSilencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape
Bidwell, B. N., Slaney, C. Y., Withana, N. P., Forster, S., Cao, Y., Loi, S., Andrews, D., Mikeska, T., Mangan, N. E., Samarajiwa, S. A., et al. (2012) · Nature Medicine · doi:10.1038/nm.2830 · Cited by 487 · see citing works
The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells
Paolino, M., Choidas, A., Wallner, S., Pranjic, B., Uribesalgo, I., Loeser, S., Jamieson, A. M., Langdon, W. Y., Ikeda, F., Fededa, J. P., et al. (2014) · Nature · doi:10.1038/nature12998 · Cited by 456 · see citing works
Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1
Vacchelli, E., Ma, Y., Baracco, E. E., Sistigu, A., Enot, D. P., Pietrocola, F., Yang, H., Adjemian, S., Chaba, K., Semeraro, M., et al. (2015) · Science · doi:10.1126/science.aad0779 · Cited by 452 · cited 1× · see citing works
“identified a loss of-function mutation in the allele of the gene coding for formyl peptide receptor 1 (Fpr1) that correlated with poor survival in breast and colorectal cancer patients receiving adjuvant chemotherapy[62].”
BackgroundMa, C., Fan, R., Ahmad, H., Shi, Q., Comin-Anduix, B., Chodon, T., Koya, R. C., Liu, C.-C., Kwong, G. A., Radu, C. G., et al. (2011) · Nature Medicine · doi:10.1038/nm.2375 · Cited by 441 · cited 1× · see citing works
“cytokine profiling, transcriptomics and proteomics of immune cells[76] [77]) to diagnose and tailor drug treatment[65], as reviewed elsewhere[45].”
Background(2000) · PubMed · Cited by 404 · see citing works
Invadopodia Are Required for Cancer Cell Extravasation and Are a Therapeutic Target for Metastasis
Leong, H. S., Robertson, A., Stoletov, K. V., Leith, S. J., Chin, C. A., Chien, A. E., Hague, M. N., Ablack, A. L., Carmine-Simmen, K., McPherson, V. A., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.07.050 · Cited by 401 · see citing works
Cheon, D., & Oršulić, S. (2011) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathol.3.121806.154244 · Cited by 397 · see citing works
Engineering microscale cellular niches for three-dimensional multicellular co-cultures
Huang, C. P., Lu, J., Seon, H., Lee, A. P., Flanagan, L. A., Kim, H.-Y., Putnam, A. J., & Jeon, N. L. (2009) · Lab on a Chip · doi:10.1039/b818401a · Cited by 384 · cited 1× · see citing works
“Furthermore, cancer cells promoted macrophage proliferation[64].”
Biological applications of microfluidic gradient devices
Kim, S., Kim, H. J., & Jeon, N. L. (2010) · Integrative Biology · doi:10.1039/c0ib00055h · Cited by 366 · cited 1× · see citing works
“, cytokines) complex gradients in the microfluidic assay in a more precise and sustained manner than in macro-scale in vitro systems[5].”
Background(1985) · PubMed · Cited by 346 · see citing works
In vitro three‐dimensional (3D) models in cancer research: An update
Kimlin, L., Casagrande, G. M. S., & Virador, V. M. (2011) · Molecular Carcinogenesis · doi:10.1002/mc.21844 · Cited by 340 · see citing works
Microfluidic Endothelium for Studying the Intravascular Adhesion of Metastatic Breast Cancer Cells
Song, J. W., Cavnar, S. P., Walker, A. C., Luker, K. E., Gupta, M., Tung, Y.-C., Luker, G. D., & Takayama, S. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005756 · Cited by 317 · see citing works
Mechanisms of tumor cell extravasation in an in vitro microvascular network platform
Chen, M. B., Whisler, J. A., Jeon, J. S., & Kamm, R. D. (2013) · Integrative Biology · doi:10.1039/c3ib40149a · Cited by 308 · cited 3× · see citing works
“In addition, μVNs replicate better the 3D vessel architecture and endothelial barrier function [21].”
BackgroundSelf-citationDeryugina, E. I., & Quigley, J. P. (2008) · Histochemistry and Cell Biology · doi:10.1007/s00418-008-0536-2 · Cited by 279 · see citing works
Apoptosis: an early event in metastatic inefficiency.
Wong, C. W., Lee, A., Shientag, L., Yu, J. H., Dong, Y., Kao, G., Al‐Mehdi, A. B., Bernhard, E. J., & Muschel, R. J. (2001) · PubMed · Cited by 276 · see citing works
Microfluidic platforms for mechanobiology
Polacheck, W. J., Li, R., Uzel, S. G. M., & Kamm, R. D. (2013) · Lab on a Chip · doi:10.1039/c3lc41393d · Cited by 272 · see citing works
Edris, B., Weiskopf, K., Volkmer, A. K., Volkmer, J.-P., Willingham, S. B., Contreras-Trujillo, H., Liu, J., Majeti, R., West, R. B., Fletcher, J. A., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1121629109 · Cited by 258 · see citing works
Control of Perfusable Microvascular Network Morphology Using a Multiculture Microfluidic System
Whisler, J. A., Chen, M. B., & Kamm, R. D. (2012) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2013.0370 · Cited by 240 · cited 1× · see citing works
“These μVNs arise from the self-organization of ECs suspended in a hydrogel in the presence of fibroblasts[25, 26] or mesenchymal stem cells[27].”
BackgroundSelf-citationIn vitro model of tumor cell extravasation
Jeon, J. S., Zervantonakis, I. K., Chung, S., Kamm, R. D., & Charest, J. L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056910 · Cited by 233 · cited 1× · see citing works
“Cancer cells are either seeded in the hydrogel for intravasation assays[18, 19] or directly perfused in the channel for extravasation[17, 20, 22] and adhesion studies[15–17].”
BackgroundSelf-citationJeon, J. S., Bersini, S., Whisler, J. A., Chen, M. B., Dubini, G., Charest, J. L., Moretti, M., & Kamm, R. D. (2014) · Integrative Biology · doi:10.1039/c3ib40267c · Cited by 229 · cited 1× · see citing works
“These μVNs arise from the self-organization of ECs suspended in a hydrogel in the presence of fibroblasts[25, 26] or mesenchymal stem cells[27].”
BackgroundSelf-citationSung, K. E., Yang, N., Pehlke, C., Keely, P. J., Eliceiri, K. W., Friedl, A., & Beebe, D. J. (2011) · Integr. Biol. · doi:10.1039/c0ib00063a · Cited by 226 · see citing works
Chemokines: role in inflammation and immune surveillance
Moser, B., & Willimann, K. (2004) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2004.028316 · Cited by 221 · cited 1× · see citing works
“For example, immune cells infiltrating tissues are recruited from the bloodstream by inflammatory chemokine/cytokine gradients[43].”
BackgroundFitzgerald, D. P., Palmieri, D., Hua, E., Hargrave, E., Herring, J. M., Qian, Y., Vega-Valle, E., Weil, R. J., Stark, A. M., Vortmeyer, A. O., et al. (2008) · Clinical & Experimental Metastasis · doi:10.1007/s10585-008-9193-z · Cited by 218 · cited 1× · see citing works
“This is particularly important as there is growing evidence that cancer cells communicate with their microenvironment[29], specifically with organ-specific cells[30], resulting in organ-selectivity in metastasis[31].”
BackgroundT cell chemotaxis in a simple microfluidic device
Lin, F., & Butcher, E. C. (2006) · Lab on a Chip · doi:10.1039/b607071j · Cited by 211 · cited 1× · see citing works
“have been used to analyze T cell[67] or neutrophil migratory behavior under chemical gradients[68]; the migration of dendritic cells, macrophages and T cells through microchannels towards bacteria[44]; the rolling of neutrophils[69] and their extravasation through endothelium[70]; or the adhesion of T cells[71] or mon…”
MethodZebrafish xenografts as a tool for in vivo studies on human cancer
Konantz, M., Balcı, T. B., Hartwig, U. F., Dellaire, G., Andre, M. C., Berman, J. N., & Lengerke, C. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06575.x · Cited by 204 · see citing works
A three-dimensional in vitro model of tumor cell intravasation
Ehsan, S. M., Welch-Reardon, K. M., Waterman, M. L., Hughes, C. C. W., & George, S. C. (2014) · Integrative Biology · doi:10.1039/c3ib40170g · Cited by 196 · cited 1× · see citing works
“Recent studies are increasingly employing microvascular networks (μVNs)[21, 23, 24], where the permeability, architecture and diameters of vessels are more similar to those found in in vivo microvascular beds (Figure 2A) [21].”
BackgroundNeurite growth in 3D collagen gels with gradients of mechanical properties
Sundararaghavan, H. G., Monteiro, G. A., Firestein, B. L., & Shreiber, D. I. (2008) · Biotechnology and Bioengineering · doi:10.1002/bit.22074 · Cited by 196 · see citing works
Zhang, S., Guo, L.-W., Chen, Q., et al. (2015) · BMC Cancer · doi:10.1186/s12885-015-1096-1 · Cited by 186 · see citing works
‘Slings’ enable neutrophil rolling at high shear
Sundd, P., Gutierrez, E., Koltsova, E. K., Kuwano, Y., Fukuda, S., Pospieszalska, M. K., Groisman, A., & Ley, K. F. (2012) · Nature · doi:10.1038/nature11248 · Cited by 181 · cited 1× · see citing works
“have been used to analyze T cell[67] or neutrophil migratory behavior under chemical gradients[68]; the migration of dendritic cells, macrophages and T cells through microchannels towards bacteria[44]; the rolling of neutrophils[69] and their extravasation through endothelium[70]; or the adhesion of T cells[71] or mon…”
MethodChip in a lab: microfluidics for next generation life science research
Streets, A. M., & Huang, Y. (2013) · Biomicrofluidics · doi:10.1063/1.4789751 · Cited by 180 · cited 1× · see citing works
“Indeed, these current “labon-a-chip” models are intended to facilitate time-consuming bench-top procedures, but are, after all, still “chips-in-a-lab”[86] that require external equipment (e.”
BackgroundJang, K., Cho, H. S., Kang, D. H., Bae, W. G., Kwon, T., & Suh, K. Y. (2010) · Integrative Biology · doi:10.1039/c0ib00018c · Cited by 177 · see citing works
Lessons from patient-derived xenografts for better in vitro modeling of human cancer
Choi, S. Y. C., Lin, D., Gout, P. W., Collins, C. C., Xu, Y., & Wang, Y. Z. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.09.009 · Cited by 174 · see citing works
Liu, S., & Leach, S. D. (2011) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130330 · Cited by 174 · see citing works
Cross talk between cancer and immune cells: exploring complex dynamics in a microfluidic environment
Businaro, L., De Ninno, A., Schiavoni, G., Lucarini, V., Ciasca, G., Gerardino, A., Belardelli, F., Gabriele, L., & Mattei, F. (2013) · Lab Chip · doi:10.1039/c2lc40887b · Cited by 162 · see citing works
Clinical microfluidics for neutrophil genomics and proteomics
Kotz, K. T., Xiao, W., Miller‐Graziano, C. L., Qian, W., Russom, A., Warner, E. A., Moldawer, L. L., De, A. K., Bankey, P. E., Petritis, B. O., et al. (2010) · Nature Medicine · doi:10.1038/nm.2205 · Cited by 161 · cited 1× · see citing works
“cytokine profiling, transcriptomics and proteomics of immune cells[76] [77]) to diagnose and tailor drug treatment[65], as reviewed elsewhere[45].”
BackgroundSung, K. E., Su, G., Pehlke, C. A., Trier, S. M., Eliceiri, K. W., Keely, P. J., Friedl, A., & Beebe, D. J. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.05.043 · Cited by 160 · see citing works
Unger, C., Kramer, N., Walzl, A., Scherzer, M., Hengstschläger, M., & Dolznig, H. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.10.015 · Cited by 158 · see citing works
A microfluidic-based device for study of transendothelial invasion of tumor aggregates in realtime
Zhang, Q., Liu, T., & Qin, J. (2012) · Lab on a Chip · doi:10.1039/c2lc00030j · Cited by 151 · cited 2× · see citing works
“Cancer cells are either seeded in the hydrogel for intravasation assays[18, 19] or directly perfused in the channel for extravasation[17, 20, 22] and adhesion studies[15–17].”
BackgroundHughes, A. J., & Herr, A. E. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1207754110 · Cited by 142 · cited 1× · see citing works
“Of note, microfluidic platforms that include such miniaturized assays on-chip are currently being developed[7, 8].”
BackgroundNew dimensions in tumor immunology: what does 3D culture reveal?
Feder-Mengus, C., Ghosh, S., Reschner, A., Martin, I., & Spagnoli, G. C. (2008) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2008.06.001 · Cited by 139 · cited 1× · see citing works
“Importantly, these studies demonstrated important differences between 2D and 3D, with tumor cells cultured in 3D spheroids showing a decreased production of TAA and HLA class I (as also observed in vivo)[47].”
BackgroundExperimental mouse tumour models: what can be learnt about human cancer immunology?
Dranoff, G. (2011) · Nature reviews. Immunology · doi:10.1038/nri3129 · Cited by 132 · cited 1× · see citing works
“Despite these limitations, mouse models remain tremendously powerful for cancer immunology research and humanized mouse models reconstituted with human dendritic cells, B or T cells are being developed[3].”
BackgroundA microfluidic platform for quantitative analysis of cancer angiogenesis and intravasation
Lee, H., Park, W., Ryu, H., & Jeon, N. L. (2014) · Biomicrofluidics · doi:10.1063/1.4894595 · Cited by 130 · cited 2× · see citing works
“Microfluidic assays have been designed to replicate certain aspects of several of these steps, such as EMT[13, 14], cancer cell invasion and adhesion[15–17], and intra-[18, 19] and extravasation[17, 20– 22] (see Text Box 3).”
BackgroundMethodMulti-step microfluidic device for studying cancer metastasis
Chaw, K. C., Manimaran, M., Tay, E. H., & Swaminathan, S. (2007) · Lab on a Chip · doi:10.1039/b707399m · Cited by 125 · see citing works
Shi, M., Majumdar, D., Gao, Y., Brewer, B. M., Goodwin, C. R., MCLEAN, J. A. J., Li, D., & Webb, D. J. (2013) · Lab on a Chip · doi:10.1039/c3lc50249j · Cited by 121 · see citing works
Pisano, M., Triacca, V., Barbee, K. A., & Swartz, M. A. (2015) · Integrative Biology · doi:10.1039/c5ib00085h · Cited by 112 · see citing works
Microfluidic model of ductal carcinoma in situ with 3D, organotypic structure
Bischel, L. L., Beebe, D. J., & Sung, K. E. (2015) · BMC Cancer · doi:10.1186/s12885-015-1007-5 · Cited by 110 · see citing works
Specificity in cancer immunotherapy
Schietinger, A., Philip, M., & Schreiber, H. W. (2008) · Seminars in Immunology · doi:10.1016/j.smim.2008.07.001 · Cited by 109 · cited 1× · see citing works
“First, because these therapies specifically target certain immune-cancer cell interactions[38], they can have lesser off-target effects.”
BackgroundPatra, B., Chen, Y.-H., Peng, C.-C., Lin, S.-C., Lee, C.-H., & Tung, Y.-C. (2013) · Biomicrofluidics · doi:10.1063/1.4824480 · Cited by 109 · see citing works
A versatile assay for monitoring in vivo-like transendothelial migration of neutrophils
Han, S., Yan, J.-J., Shin, Y., Jeon, J. S., Won, J., Jeong, H. E., Kamm, R. D., Kim, Y., & Chung, S. H. (2012) · Lab on a Chip · doi:10.1039/c2lc40445a · Cited by 104 · cited 1× · see citing works
“have been used to analyze T cell[67] or neutrophil migratory behavior under chemical gradients[68]; the migration of dendritic cells, macrophages and T cells through microchannels towards bacteria[44]; the rolling of neutrophils[69] and their extravasation through endothelium[70]; or the adhesion of T cells[71] or mon…”
MethodSelf-citationMicrofluidic squeezing for intracellular antigen loading in polyclonal B-cells as cellular vaccines
Szeto, G. L., Egeren, D. V., Worku, H. A., Sharei, A., Alejandro, B. S., Park, C., Frew, K., Brefo, M. S. N., Mao, S., Heimann, M., et al. (2015) · Scientific Reports · doi:10.1038/srep10276 · Cited by 98 · cited 1× · see citing works
“This was achieved by forcing the cells through a narrow channel, transiently disrupting their membranes and allowing intracellular delivery of proteins from the surrounding media through the membrane[80].”
A microdevice for multiplexed detection of T-cell-secreted cytokines
Zhu, H., Stybayeva, G., Macal, M., et al. (2008) · Lab on a Chip · doi:10.1039/b810244a · Cited by 98 · see citing works
Trkov, S., Eng, G. M., Liddo, R. D., Parnigotto, P. P., & Vunjak‐Novakovic, G. (2009) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.231 · Cited by 98 · see citing works
Microfluidic single-cell analysis for systems immunology
Junkin, M., & Tay, S. (2014) · Lab on a Chip · doi:10.1039/c3lc51182k · Cited by 96 · cited 4× · see citing works
“Although these devices have better potential for high throughput testing than animal studies, many current microfluidic platforms depend heavily on high resolution imaging and similarly time-consuming image and data analysis[45].”
BackgroundMethodInfluentialShin, M. K., Kim, S. K., & Jung, H. (2011) · Lab on a Chip · doi:10.1039/c1lc20671k · Cited by 94 · see citing works
Nesmith, A. P., Agarwal, A., McCain, M. L., & Parker, K. K. (2014) · Lab on a Chip · doi:10.1039/c4lc00688g · Cited by 93 · see citing works
Cancer-driven dynamics of immune cells in a microfluidic environment
Agliari, E., Biselli, E., De Ninno, A., Schiavoni, G., Gabriele, L., Gerardino, A., Mattei, F., Barra, A., & Businaro, L. (2014) · Scientific Reports · doi:10.1038/srep06639 · Cited by 91 · cited 1× · see citing works
“They observed the migration of macrophages towards cancer cells [48] and tested different chemotherapy treatments in the microfluidic device.”
Background“In vitro” 3D models of tumor-immune system interaction
Hirt, C., Papadimitropoulos, A., Mele, V., Muraro, M. G., Mengus, C., Iezzi, G., Terracciano, L., Martín, I., & Spagnoli, G. C. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.05.003 · Cited by 90 · cited 3× · see citing works
“Importantly, these studies demonstrated important differences between 2D and 3D, with tumor cells cultured in 3D spheroids showing a decreased production of TAA and HLA class I (as also observed in vivo)[47].”
BackgroundMicrofluidic analysis of pressure drop and flow behavior in hypertensive micro vessels
Hu, R., Li, F., Lv, J., He, Y., Lu, D., Yamada, T., & Ono, N. (2015) · Biomedical Microdevices · doi:10.1007/s10544-015-9959-4 · Cited by 83 · see citing works
Immunotherapy for metastatic solid cancers
Turcotte, S., & Rosenberg, S. A. (2011) · Advances in Surgery · doi:10.1016/j.yasu.2011.04.003 · Cited by 81 · cited 1× · see citing works
“Recently, immunotherapies have shown promising results for reducing metastasis in melanoma or kidney cancer patients[1, 2].”
BackgroundToward the broad adoption of 3D tumor models in the cancer drug pipeline
Cox, M. C., Reese, L. M., Bickford, L. R., & Verbridge, S. S. (2015) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.5b00172 · Cited by 80 · cited 1× · see citing works
“Yet, challenges remain before microfluidic assays can be routinely used in the clinic [82, 83] (Outstanding Question Box) [84].”
MethodThe importance of animal models in tumor immunity and immunotherapy
Budhu, S., Wolchok, J. D., & Merghoub, T. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2013.11.008 · Cited by 78 · cited 1× · see citing works
“The importance of the role of immune cells in cancer was revealed, amongst other pioneering studies, by William Coley in the late 1800s, when he observed tumor remission in patients with bacterial infections[35, 36].”
ResultHigh-Resolution Multiphoton Imaging of Tumors In VivoPreprint
Wyckoff, J. B., Gligorijevic, B., Entenberg, D. R., Segall, J. E., & Condeelis, J. S. (2011) · Cold Spring Harbor Protocols · doi:10.1101/pdb.top065904 · Cited by 72 · see citing works
In vitro models of the metastatic cascade: from local invasion to extravasation
Bersini, S., Jeon, J. S., Moretti, M., & Kamm, R. D. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2013.12.006 · Cited by 71 · cited 1× · see citing works
“One of the major current limitations of in vitro metastatic models is their lack of organspecificity[28].”
BackgroundSelf-citationAn integrated microfluidic platform for in situ cellular cytokine secretion immunophenotyping
Huang, N., Chen, W., Oh, B., Cornell, T. T., Shanley, T. P., Fu, J., & Kurabayashi, K. (2012) · Lab on a Chip · doi:10.1039/c2lc40619e · Cited by 69 · see citing works
A bladder cancer microenvironment simulation system based on a microfluidic co-culture model
Liu, P.-F., Cao, Y.-W., Zhang, S.-D., Zhao, Y., Liu, X.-G., Shi, H.-Q., Hu, K.-Y., Zhu, G.-Q., Ma, B., & Niu, H.-T. (2015) · Oncotarget · doi:10.18632/oncotarget.6070 · Cited by 68 · see citing works
A microfluidic membrane device to mimic critical components of the vascular microenvironment
Srigunapalan, S., Lam, C. J., Wheeler, A. R., & Simmons, C. A. (2011) · Biomicrofluidics · doi:10.1063/1.3530598 · Cited by 67 · cited 1× · see citing works
“have been used to analyze T cell[67] or neutrophil migratory behavior under chemical gradients[68]; the migration of dendritic cells, macrophages and T cells through microchannels towards bacteria[44]; the rolling of neutrophils[69] and their extravasation through endothelium[70]; or the adhesion of T cells[71] or mon…”
MethodCooperative actions of p21WAF1 and p53 induce Slug protein degradation and suppress cell invasion
Kim, J., Bae, S., An, S., Park, J. K., Kim, E. M., Hwang, S., Kim, W., & Um, H. (2014) · EMBO Reports · doi:10.15252/embr.201438587 · Cited by 66 · see citing works
Modeling of cancer metastasis and drug resistance via biomimetic nano-cilia and microfluidics
Kuo, C.-T., Chiang, C.-L., Chang, C.-H., Liu, H.-K., Huang, G.-S., Huang, R. Y.-J., Lee, H., Huang, C.-S., & Wo, A. M. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2013.11.008 · Cited by 65 · cited 5× · see citing works
“Note that we show intravasation for a single cancer cell, but future models should also consider intravasation from a multi-cellular tumor mass, as has been done in a non-microfluidic 3D model [23]: i) Spheroid of GFP-MCF-7 labelled cells to model epithelial to mesenchymal transition (EMT), where the dashed circle sho…”
MethodInfluentialA microfluidic model for organ-specific extravasation of circulating tumor cells
Riahi, R., Yang, Y. L., Kim, H., Jiang, L., Wong, P. K., & Zohar, Y. (2014) · Biomicrofluidics · doi:10.1063/1.4868301 · Cited by 60 · cited 1× · see citing works
“Cancer cells are either seeded in the hydrogel for intravasation assays[18, 19] or directly perfused in the channel for extravasation[17, 20, 22] and adhesion studies[15–17].”
BackgroundA microfluidic device to study cancer metastasis under chronic and intermittent hypoxia
Acosta, M. A., Jiang, X., Huang, P.-K., Cutler, K. B., Grant, C., Walker, G. M., & Gamcsik, M. P. (2014) · Biomicrofluidics · doi:10.1063/1.4898788 · Cited by 58 · see citing works
Mattei, F., Schiavoni, G., De Ninno, A., Lucarini, V., Sestili, P., Sistigu, A., Fragale, A., Sanchez, M., Spada, M., Gerardino, A., et al. (2014) · Journal of Immunotoxicology · doi:10.3109/1547691x.2014.891677 · Cited by 57 · cited 1× · see citing works
“more tumors with less immune cell infiltration than wild type animals[50], and subsequently used a microfluidic assay to investigate the underlying mechanism in greater detail.”
MethodKim, J., Wong, C. W., Goldsmith, J. D., Song, C. H., Fu, W., Allion, M.-B., Herlyn, M., Al‐Mehdi, A. B., & Muschel, R. J. (2004) · Cancer Letters · doi:10.1016/j.canlet.2004.03.042 · Cited by 49 · see citing works
Chen, W., Huang, N., Oh, B., Lam, R. H. W., Fan, R., Cornell, T. T., Shanley, T. P., Kurabayashi, K., & Fu, J. (2013) · Advanced Healthcare Materials · doi:10.1002/adhm.201200378 · Cited by 48 · see citing works
Hsu, T.-H., Kao, Y.-L., Lin, W.-L., Xiao, J.-L., Kuo, P.-L., Wu, C.-W., Liao, W.-Y., & Lee, C.-H. (2012) · Integr. Biol. · doi:10.1039/c2ib00112h · Cited by 47 · cited 1× · see citing works
“This study provides insight into tumor-stroma interactions and also into the crosstalk between different types of stromal cells and combinatorial effects on cancer cells[51].”
BackgroundGopalakrishnan, N., Hannam, R., Casoni, G. P., Barriet, D., Ribe, J. M., Haug, M., & Halaas, Ø. (2015) · Lab on a Chip · doi:10.1039/c4lc01438c · Cited by 42 · cited 2× · see citing works
“It is the ability to establish such precise gradients in microfluidic devices that makes them useful for studying immune cell responses in vitro[44].”
BackgroundMethodIn vitro micro-physiological models for translational immunology
Ramadan, Q., & Gijs, M. A. M. (2015) · Lab on a Chip · doi:10.1039/c4lc01271b · Cited by 41 · cited 3× · see citing works
“Similarly, organ-specific cells could be added, eventually leading to “bodyon-a-chip” platforms, wherein multiple organs are mimicked in different compartments of a single microfluidic device and connected via channels, recapitulating the systemic nature of the metastatic process [66].”
BackgroundMethodA standalone perfusion platform for drug testing and target validation in micro-vessel networks
Zhang, B., Peticone, C., Murthy, S. K., & Radisic, M. (2013) · Biomicrofluidics · doi:10.1063/1.4818837 · Cited by 39 · see citing works
Shin, Y., Kim, H., Han, S., Won, J., Jeong, H. E., Lee, E. S., Kamm, R. D., Kim, J., & Chung, S. H. (2012) · Advanced Healthcare Materials · doi:10.1002/adhm.201200320 · Cited by 38 · see citing works
Self-citationImplementation of microfluidic sandwich ELISA for superior detection of plant pathogens
Thaitrong, N., Charlermroj, R., Himananto, O., Seepiban, C., & Karoonuthaisiri, N. (2013) · PLoS ONE · doi:10.1371/journal.pone.0083231 · Cited by 34 · cited 1× · see citing works
“Of note, microfluidic platforms that include such miniaturized assays on-chip are currently being developed[7, 8].”
BackgroundKim, S. K., Moon, W. K., Park, J. Y., & Jung, H. (2012) · The Analyst · doi:10.1039/c2an35424a · Cited by 34 · cited 1× · see citing works
“have been used to analyze T cell[67] or neutrophil migratory behavior under chemical gradients[68]; the migration of dendritic cells, macrophages and T cells through microchannels towards bacteria[44]; the rolling of neutrophils[69] and their extravasation through endothelium[70]; or the adhesion of T cells[71] or mon…”
MethodBacteriology: A caring culture
DeWeerdt, S. (2013) · Nature · doi:10.1038/504s4a · Cited by 31 · cited 1× · see citing works
“The importance of the role of immune cells in cancer was revealed, amongst other pioneering studies, by William Coley in the late 1800s, when he observed tumor remission in patients with bacterial infections[35, 36].”
ResultChen, W., Huang, N.-T., Li, X., Yu, Z. T. F., Kurabayashi, K., & Fu, J. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00098 · Cited by 31 · cited 2× · see citing works
“Microfluidic models have been more widely used for studying immunology, outside of cancer research, as discussed extensively in other reviews[45, 65, 66].”
BackgroundMethodIn vitro models of the metastatic cascade: from local invasion to extravasation
Bersini, S., Moretti, M., Jeon, J. S., & Kamm, R. D. (2014) · DSpace@MIT (Massachusetts Institute of Technology) · Cited by 25 · see citing works
Self-citationKuo, C.-T., Liu, H.-K., Huang, G.-S., Chang, C.-H., Chen, C.-L., Chen, K.-C., Yun-Ju Huang, R., Lin, C.-H., Lee, H., Huang, C.-S., et al. (2014) · The Analyst · doi:10.1039/c4an00936c · Cited by 20 · cited 5× · see citing works
“Note that we show intravasation for a single cancer cell, but future models should also consider intravasation from a multi-cellular tumor mass, as has been done in a non-microfluidic 3D model [23]: i) Spheroid of GFP-MCF-7 labelled cells to model epithelial to mesenchymal transition (EMT), where the dashed circle sho…”
MethodInfluentialNeutrophil migration under spatially-varying chemoattractant gradient profiles
Halilovic, I., Wu, J., Alexander, M. E., & Lin, F. (2015) · Biomedical Microdevices · doi:10.1007/s10544-015-9963-8 · Cited by 15 · cited 1× · see citing works
“have been used to analyze T cell[67] or neutrophil migratory behavior under chemical gradients[68]; the migration of dendritic cells, macrophages and T cells through microchannels towards bacteria[44]; the rolling of neutrophils[69] and their extravasation through endothelium[70]; or the adhesion of T cells[71] or mon…”
Method
Flagged first, then by citations
6 of the 127 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Organ-on-a-Chip: A New Paradigm for Drug Development
Ma, C., Peng, Y., Li, H., & Chen, W. (2020) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.11.009 · Cited by 589 · see citing works
Hoarau-Véchot, J., Rafii, A., Touboul, C., & Pasquier, J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19010181 · Cited by 489 · see citing works
“If further analysis (Elisa, western blot) is required, the low cell number can also present a drawback [67].”
3D bioprinting for reconstituting the cancer microenvironment
Datta, P., Dey, M., Ataie, Z., Unutmaz, D., & Ozbolat, I. T. (2020) · npj Precision Oncology · doi:10.1038/s41698-020-0121-2 · Cited by 314 · see citing works
Personalized Cancer Medicine: An Organoid Approach
Es, H. A., Montazeri, L., Aref, A. R., Vosough, M., & Baharvand, H. (2018) · Trends in biotechnology · doi:10.1016/j.tibtech.2017.12.005 · Cited by 277 · see citing works
“In contrast to 2D cancer–immune interaction, in vitro 3D studies not only demonstrated decreased production of tumor-associated antigens in 3D models, but also highlighted the importance of using 3D tumor models in tumor immunology studies, which can be easily captured in microfluidic systems [64].”
BackgroundMoshksayan, K., Kashaninejad, N., Warkiani, M. E., Lock, J. G., Moghadas, H., Firoozabadi, B., Saidi, M. S., & Nguyen, N.-T. (2018) · Sensors and Actuators B: Chemical · doi:10.1016/j.snb.2018.01.223 · Cited by 267 · see citing works
“Other works have reviewed the importance of microfluidics in cancer cell culture and drug discovery [74-80], as well as considering various microfluidic chips enabling 3D cell culture with cancerous or noncancerous cells [9, 81-86].”
BackgroundTargeting immune cells for cancer therapy
Gun, S. Y., Lee, S. W. L., Sieow, J. L., & Wong, S. C. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101174 · Cited by 229 · see citing works
Self-citationOrgan-on-chip models of cancer metastasis for future personalized medicine: From chip to the patient
Caballero, D., Kaushik, S., Correlo, V. M., Oliveira, J. M., Reis, R. L., & Kundu, S. C. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.10.005 · Cited by 221 · see citing works
A role for microfluidic systems in precision medicine
Ayuso, J. M., Virumbrales-Muñoz, M., Lang, J. M., & Beebe, D. J. (2022) · Nature Communications · doi:10.1038/s41467-022-30384-7 · Cited by 216 · see citing works
Organ-on-a-Chip for Cancer and Immune Organs Modeling
Sun, W., Luo, Z., Lee, J., Kim, H., Lee, K., Tebon, P., Feng, Y., Dokmeci, M. R., Sengupta, S., & Khademhosseini, A. (2019) · Advanced Healthcare Materials · doi:10.1002/adhm.201801363 · Cited by 221 · see citing works
Dynamic interplay between tumour, stroma and immune system can drive or prevent tumour progression
Seager, R. J., Hajal, C., Spill, F., Kamm, R. D., & Zaman, M. H. (2017) · Convergent Science Physical Oncology · doi:10.1088/2057-1739/aa7e86 · Cited by 185 · see citing works
“The mechanical properties of the ECM have a significant effect on cancer dissemination and immune cell-cancer cell interactions, and furthermore, immune cells have been shown to play a role in various steps of the metastatic cascade, from cancer cell detachment and dissemination from the primary tumour, to their arres…”
Self-citationParlato, S., De Ninno, A., Molfetta, R., Toschi, E., Salerno, D., Mencattini, A., Romagnoli, G., Fragale, A., Roccazzello, L., Buoncervello, M., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-01013-x · Cited by 181 · see citing works
Ayuso, J. M., Rehman, S., Virumbrales-Muñoz, M., McMinn, P. H., Geiger, P. G., Fitzgerald, C., Heaster, T. M., Skala, M. C., & Beebe, D. J. (2021) · Science Advances · doi:10.1126/sciadv.abc2331 · Cited by 174 · see citing works
“Therefore, the development of new tools that allow researchers to decipher the complex mechanisms driving immune exhaustion could accelerate the development of next-generation immunotherapies (12).”
BackgroundThe effects of monocytes on tumor cell extravasation in a 3D vascularized microfluidic model
Boussommier-Calleja, A., Atiyas, Y., Haase, K., Headley, M., Lewis, C., & Kamm, R. D. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2018.03.005 · Cited by 158 · see citing works
“We have established microfluidic devices as a unique and powerful platform for studying immune and cancer cell dynamics, in particular during the metastatic cascade[23].”
MethodSelf-citationTumor organoid models in precision medicine and investigating cancer-stromal interactions
Xu, R., Zhou, X., Wang, S., & Trinkle, C. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107668 · Cited by 134 · see citing works
Endothelial Regulation of Drug Transport in a 3D Vascularized Tumor Model
Haase, K., Offeddu, G. S., Gillrie, M. R., & Kamm, R. D. (2020) · Advanced Functional Materials · doi:10.1002/adfm.202002444 · Cited by 126 · see citing works
Self-citationMicroengineered cancer-on-a-chip platforms to study the metastatic microenvironment
Lara, R. P., & Annabi, N. (2016) · Lab on a Chip · doi:10.1039/c6lc00718j · Cited by 128 · see citing works
Applications of tumor chip technology
Hachey, S. J., & Hughes, C. C. W. (2018) · Lab on a Chip · doi:10.1039/c8lc00330k · Cited by 128 · see citing works
Applications of Microfluidics and Organ-on-a-Chip in Cancer Research
Regmi, S., Poudel, C., Adhikari, R., & Luo, K. Q. (2022) · Biosensors · doi:10.3390/bios12070459 · Cited by 126 · see citing works
Brain-on-a-chip: A history of development and future perspective
Bang, S., Jeong, S., Choi, N., & Kim, H. N. (2019) · Biomicrofluidics · doi:10.1063/1.5120555 · Cited by 115 · see citing works
Tumor Cell Dormancy: Threat or Opportunity in the Fight against Cancer
Jahanban-Esfahlan, R., Seidi, K., Manjili, M. H., Jahanban-Esfahlan, A., Javaheri, T., & Zare, P. (2019) · Cancers · doi:10.3390/cancers11081207 · Cited by 111 · see citing works
Characterizing the role of monocytes in T cell cancer immunotherapy using a 3d microfluidic model
Lee, S. W. L., Adriani, G., Ceccarello, E., Pavesi, A., Tan, A. T., Bertoletti, A., Kamm, R. D., & Wong, S. C. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00416 · Cited by 109 · see citing works
“Prompted by our null observations in a 2D system, we moved toward a 3D microfluidic tumor model, which, among several other advantages, is a physiological improvement from the 2D in vitro system (43, 45).”
MethodSelf-citationKuo, C., Wang, J.-Y., Lin, Y., Wo, A. M., Chen, B. P. C., & Lee, H. (2017) · Scientific Reports · doi:10.1038/s41598-017-04718-1 · Cited by 108 · see citing works
Wang, X., Sun, Q., & Pei, J. (2018) · Micromachines · doi:10.3390/mi9100493 · Cited by 106 · see citing works
“Besides the anti-angiogenic therapies, immunotherapies against cancer have shown enormous potential, leading to the recent FDA approval of several drugs that reduce cancer progression [138].”
BackgroundModeling Nanocarrier Transport across a 3D In Vitro Human Blood‐Brain–Barrier Microvasculature
Lee, S. W. L., Campisi, M., Osaki, T., Possenti, L., Mattu, C., Adriani, G., Kamm, R. D., & Chiono, V. (2020) · Advanced Healthcare Materials · doi:10.1002/adhm.201901486 · Cited by 103 · see citing works
Self-citationDrug screening in 3D in vitro tumor models: overcoming current pitfalls of efficacy read‐outs
Santo, V. E., Rebelo, S. P., Estrada, M. F., Alves, P. M., Boghaert, E. R., & Brito, C. (2016) · Biotechnology Journal · doi:10.1002/biot.201600505 · Cited by 103 · see citing works
“Therefore, these microfluidic models constitute ideal setups to test libraries of compounds and biological formulations [112].”
BackgroundAdvanced model systems and tools for basic and translational human immunology
Wagar, L. E., DiFazio, R. M., & Davis, M. M. (2018) · Genome Medicine · doi:10.1186/s13073-018-0584-8 · Cited by 102 · see citing works
Towards the development of human immune-system-on-a-chip platforms
Polini, A., del Mercato, L. L., Adriano Barra, A., Zhang, Y. S., Calabi, F., & Gigli, G. (2018) · Drug Discovery Today · doi:10.1016/j.drudis.2018.10.003 · Cited by 98 · see citing works
3D cancer models: One step closer to in vitro human studies
Manduca, N., Maccafeo, E., Maria, R. D., Sistigu, A., & Musella, M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1175503 · Cited by 95 · see citing works
Microphysiological Systems: Design, Fabrication, and Applications
Wang, K., Man, K., Liu, J., Liu, Y., Chen, Q., Zhou, Y., & Yang, Y. S. (2020) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.9b01667 · Cited by 83 · see citing works
Immunocompetent cancer-on-chip models to assess immuno-oncology therapy
Maulana, T. I., Kromidas, E., Wallstabe, L., Cipriano, M., Alb, M., Zaupa, C., Hudecek, M., Fogal, B., & Loskill, P. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.03.015 · Cited by 82 · see citing works
In Vitro Modeling of Mechanics in Cancer Metastasis
Malandrino, A., Kamm, R. D., & Moeendarbary, E. (2017) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.7b00041 · Cited by 78 · see citing works
Self-citationIn vitro models of molecular and nano-particle transport across the blood-brain barrier
Hajal, C., Campisi, M., Mattu, C., Chiono, V., & Kamm, R. D. (2018) · Biomicrofluidics · doi:10.1063/1.5027118 · Cited by 77 · see citing works
Self-citationA microfluidic platform for drug screening in a 3D cancer microenvironment
Pandya, H. J., Dhingra, K., Prabhakar, D., Chandrasekar, V., Natarajan, S. K., Vasan, A. S., Kulkarni, A., & Shafiee, H. (2017) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2017.03.054 · Cited by 76 · see citing works
“In the past decade, microfluidics has shown a great promise in developing tools for cancer research (Mukhopadhyay, 2007; Calleja et al., 2016; Wlodkowic and Cooper, 2010).”
BackgroundYang, Y., Hu, Y., & Wang, H. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/5274084 · Cited by 76 · see citing works
“Given its advantages of high-throughput feature, controllable tumor growth for standardization, and patient-derived cell growth allowing for personalized medicine [119–121], in vitro 3D tissue model by tissue engineering technology such as microfluidic technique could be a powerful alternative approach for the study o…”
BackgroundHow single-cell immunology is benefiting from microfluidic technologies
Jammes, F., & Maerkl, S. J. (2020) · Microsystems & Nanoengineering · doi:10.1038/s41378-020-0140-8 · Cited by 73 · see citing works
Ronteix, G., Jain, S., Angély, C., Cazaux, M., Khazen, R., Bousso, P., & Baroud, C. N. (2022) · Nature Communications · doi:10.1038/s41467-022-30575-2 · Cited by 71 · see citing works
“(11), (12), and (13), provides a formula for λin(n): λinðnÞ 1⁄4 logð1 pn;nþ1Þ ðN nÞΔt : ð14Þ”
Beer, M., Kuppalu, N., Stefanini, M., Becker, H., Schulz, I., Manoli, S., Schuette, J., Schmees, C., Casazza, A., Stelzle, M., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-01256-8 · Cited by 75 · see citing works
Emerging approaches to study cell-cell interactions in tumor microenvironment
Nishida‐Aoki, N., & Gujral, T. S. (2019) · Oncotarget · doi:10.18632/oncotarget.26585 · Cited by 75 · see citing works
“These microchambers allow observation of real-time and 3D immune-cancer cell interactions [75], cell behavior in metastatic cascades, such as EMT, invasion and adhesion for intra-and extravasation [76].”
BackgroundLucarini, V., Buccione, C., Ziccheddu, G., Peschiaroli, F., Sestili, P., Puglisi, R., Mattia, G., Zanetti, C., Parolini, I., Bracci, L., et al. (2016) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2016.08.024 · Cited by 73 · see citing works
Microfluidic Systems for Cancer Diagnosis and Applications
Akgönüllü, S., Bakhshpour, M., Pişkin, A. K., & Deni̇zli̇, A. (2021) · Micromachines · doi:10.3390/mi12111349 · Cited by 71 · see citing works
“A variety of in vivo, ex vivo, and in vitro experimental models have been traditionally used to discover therapeutic targets and test novel drugs for cancer [55].”
BackgroundMethodInflammation-on-a-Chip: Probing the Immune System Ex Vivo
Irimia, D., & Wang, X. (2018) · Trends in biotechnology · doi:10.1016/j.tibtech.2018.03.011 · Cited by 73 · see citing works
Ekert, J. E., Deakyne, J., Pribul-Allen, P., Terry, R., Schofield, C., Jeong, C. G., Storey, J., Mohamet, L., Francis, J., Naidoo, A., et al. (2020) · SLAS DISCOVERY · doi:10.1177/2472555220923332 · Cited by 68 · see citing works
Advanced technological tools to study multidrug resistance in cancer
Andrei, L., Kasas, S., Ochoa, I., Stanković, T., Korsnes, M. S., Václavíková, R., Assaraf, Y. G., & Pešić, M. (2019) · Drug Resistance Updates · doi:10.1016/j.drup.2019.100658 · Cited by 67 · see citing works
“several approaches using different microfluidic devices to mimic the immune-cancer interactions were developed (Boussommier-Calleja et al., 2016).”
BackgroundBiomechanical Contributions to Macrophage Activation in the Tumor Microenvironment
Hoffmann, E. J., & Ponik, S. M. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00787 · Cited by 68 · see citing works
Microfluidics meets 3D cancer cell migration
Mehta, P., Rahman, Z., ten Dijke, P., & Boukany, P. E. (2022) · Trends in cancer · doi:10.1016/j.trecan.2022.03.006 · Cited by 72 · see citing works
Kumar, V., & Varghese, S. (2018) · Advanced Healthcare Materials · doi:10.1002/adhm.201801198 · Cited by 68 · see citing works
A 3D toolbox to enhance physiological relevance of human tissue models
Picollet-D’hahan, N., Dolega, M. E., Liguori, L., Marquette, C., Le Gac, S., Gidrol, X., & Martin, D. K. (2016) · Trends in Biotechnology · doi:10.1016/j.tibtech.2016.06.012 · Cited by 65 · see citing works
Tumor-on-a-chip platforms to study cancer–immune system crosstalk in the era of immunotherapy
Parlato, S., Grisanti, G., Sinibaldi, G., Peruzzi, G., Casciola, C. M., & Gabriele, L. (2020) · Lab on a Chip · doi:10.1039/d0lc00799d · Cited by 67 · see citing works
Saha, B., Mathur, T., Handley, K. F., Hu, W., Afshar-Kharghan, V., Sood, A. K., & Jain, A. (2020) · Blood Advances · doi:10.1182/bloodadvances.2020001632 · Cited by 63 · see citing works
“hypotheses and dissect the events underlying human platelet extravasation with animal models is not easily possible.(12) For example, determining vascular alterations near cancer tissue over time is extremely challenging, and differential tissue and cell effluents cannot be continually collected for downstream genetic…”
BackgroundNew Advances in the Study of Bone Tumors: A Lesson From the 3D Environment
Cortini, M., Baldini, N., & Avnet, S. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00814 · Cited by 64 · see citing works
Lee, S. W. L., Seager, R. J., Litvak, F., Spill, F., Sieow, J. L., Leong, P. H., Kumar, D., Tan, A. S. M., Wong, S. C., Adriani, G., et al. (2020) · Integrative Biology · doi:10.1093/intbio/zyaa007 · Cited by 60 · see citing works
Self-citationDegradation of extracellular matrix regulates osteoblast migration: A microfluidic-based study
Movilla, N., Borau, C., Valero, C., & García‐Aznar, J. M. (2017) · Bone · doi:10.1016/j.bone.2017.10.025 · Cited by 62 · see citing works
Screening Cancer Immunotherapy: When Engineering Approaches Meet Artificial Intelligence
Zhou, X., Qu, M., Tebon, P. J., Jiang, X., Wang, C., Xue, Y., Zhu, J., Zhang, S., Öklü, R., Sengupta, S., et al. (2020) · Advanced Science · doi:10.1002/advs.202001447 · Cited by 54 · see citing works
Microfluidic modeling of the biophysical microenvironment in tumor cell invasion
Huang, Y., Segall, J. E., & Wu, M. (2017) · Lab on a Chip · doi:10.1039/c7lc00623c · Cited by 55 · see citing works
Tumor Microenvironment and Hydrogel-Based 3D Cancer Models for In Vitro Testing Immunotherapies
Vitale, C., Marzagalli, M., Scaglione, S., Dondero, A., Bottino, C., & Castriconi, R. (2022) · Cancers · doi:10.3390/cancers14041013 · Cited by 54 · see citing works
“Interestingly, at this time, the majority of these microfluidic devices are adopted for co-culturing tumor–immune cells in different compartments, physically separated by a polymeric gel, for evaluating the real-time cell migration under virtual static conditions, similar to the Boyden chamber-based assays [204,206,20…”
BackgroundMethodInfluentialJain, K. K. (2020) · Medical Principles and Practice · doi:10.1159/000511107 · Cited by 48 · see citing works
Macaraniag, C., Luan, Q., Zhou, J., & Papautsky, I. (2022) · APL Bioengineering · doi:10.1063/5.0093806 · Cited by 46 · see citing works
Mitxelena‐Iribarren, O., Zabalo, J., Arana, S., & Mujika, M. (2018) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2018.09.001 · Cited by 45 · see citing works
Critical Considerations for the Design of Multi-Organ Microphysiological Systems (MPS)
Malik, M., Yang, Y., Fathi, P., Mahler, G. J., & Esch, M. B. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.721338 · Cited by 43 · see citing works
Flourishing tumor organoids: History, emerging technology, and application
Yang, Q., Li, M., Yang, X., Xiao, Z., Tong, X., Tuerdi, A., Li, S., & Lei, L. (2023) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10559 · Cited by 45 · see citing works
Fluid flow to mimic organ function in 3D in vitro models
Juste-Lanas, Y., Hervás-Raluy, S., García‐Aznar, J. M., & González‐Loyola, A. (2023) · APL Bioengineering · doi:10.1063/5.0146000 · Cited by 50 · see citing works
Assessing personalized responses to anti-PD-1 treatment using patient-derived lung tumor-on-chip
Veith, I., Nurmik, M., Mencattini, A., Damei, I., Lansche, C., Brosseau, S., Gropplero, G., Corgnac, S., Filippi, J., Poté, N., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101549 · Cited by 49 · see citing works
“3,5 For example, we previously showed that a specific immune response, antibody-dependent cell-mediated cytotoxicity, can be recapitulated in a HER2 + breast ToC treated with trastuzumab (Herceptin).”
BackgroundOncoimmunology Meets Organs-on-Chip
Mattei, F., Andreone, S., Mencattini, A., Ninno, A. D., Businaro, L., Martinelli, E., & Schiavoni, G. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.627454 · Cited by 46 · see citing works
“Thus, OOC systems can be classified as advanced in vitro smart platforms evolved from in vitro and in vivo scientific knowledge (Boussommier-Calleja et al., 2016).”
BackgroundTan, S. Y., Leung, Z., & Wu, A. R. (2020) · Small · doi:10.1002/smll.201905055 · Cited by 44 · see citing works
Microphysiological systems for solid tumor immunotherapy: opportunities and challenges
Abizanda-Campo, S., Virumbrales-Muñoz, M., Humayun, M., Mármol, I., Beebe, D. J., Ochoa, I., Oliván, S., & Ayuso, J. M. (2023) · Microsystems & Nanoengineering · doi:10.1038/s41378-023-00616-x · Cited by 41 · see citing works
Microfluidic system for modelling 3D tumour invasion into surrounding stroma and drug screening
Du, Z., Mi, S., Yi, X., Xu, Y., & Sun, W. (2018) · Biofabrication · doi:10.1088/1758-5090/aac70c · Cited by 42 · see citing works
Ayensa-Jiménez, J., Pérez-Aliacar, M., Ranđelović, T., Oliván, S., Fernández, L. J., Sanz‐Herrera, J. A., Ochoa, I., Doweidar, M. H., & Doblaré, M. (2020) · Scientific Reports · doi:10.1038/s41598-020-78215-3 · Cited by 39 · see citing works
Incorporating Tumor-Associated Macrophages into Engineered Models of Glioma
Akins, E. A., Aghi, M. K., & Kumar, S. (2020) · iScience · doi:10.1016/j.isci.2020.101770 · Cited by 39 · see citing works
“platforms have proven useful for studying cell migration, angiogenesis and other cancer-associated phenomena, and are increasingly being leveraged to model cancerimmune cell interactions (Boussommier-Calleja et al., 2016; Ma et al., 2018; Sung and Beebe, 2014).”
BackgroundRingquist, R., Ghoshal, D., Jain, R., & Roy, K. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114003 · Cited by 39 · see citing works
Ravi, K., Manoharan, T. J. M., Wang, K.-C., Pockaj, B. A., & Nikkhah, M. (2023) · Biomaterials · doi:10.1016/j.biomaterials.2023.122428 · Cited by 42 · see citing works
Offeddu, G. S., Cambria, E., Shelton, S. E., Haase, K., Wan, Z., Possenti, L., Nguyen, H. T., Gillrie, M. R., Hickman, D., Knutson, C. G., et al. (2024) · Advanced Science · doi:10.1002/advs.202402757 · Cited by 36 · see citing works
Self-citationDhiman, N., Shagaghi, N., Bhave, M. R., Sümer, H., Kingshott, P., & Rath, S. N. (2020) · Cytotherapy · doi:10.1016/j.jcyt.2020.07.004 · Cited by 36 · see citing works
Going with the Flow: Modeling the Tumor Microenvironment Using Microfluidic Technology
Xie, H., Appelt, J. W., & Jenkins, R. W. (2021) · Cancers · doi:10.3390/cancers13236052 · Cited by 39 · see citing works
Organoids Provide an Important Window on Inflammation in Cancer
Baker, K. (2018) · Cancers · doi:10.3390/cancers10050151 · Cited by 35 · see citing works
Tissues and Tumor Microenvironment (TME) in 3D: Models to Shed Light on Immunosuppression in Cancer
Ho, T., & Msallam, R. (2021) · Cells · doi:10.3390/cells10040831 · Cited by 37 · see citing works
Modeling the Leukemia Microenviroment In Vitro
Scielzo, C., & Ghia, P. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.607608 · Cited by 33 · see citing works
“Many models recently developed include vasculature components that allow angiogenesis and migration (48).”
BackgroundMethodChen, S.-C., Wu, P.-C., Wang, C.-Y., & Kuo, P.-L. (2020) · Scientific Reports · doi:10.1038/s41598-020-70694-8 · Cited by 31 · see citing works
Hot or cold: Bioengineering immune contextures into in vitro patient-derived tumor models
Too, N. S. H., Ho, N. C. W., Adine, C., Iyer, N. G., & Fong, E. L. S. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.05.001 · Cited by 31 · see citing works
Towards in silico Models of the Inflammatory Response in Bone Fracture Healing
Lafuente-Gracia, L., Borgiani, E., Nasello, G., & Geris, L. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.703725 · Cited by 32 · see citing works
Engineered fluidic systems to understand lymphatic cancer metastasis
Greenlee, J. D., & King, M. R. (2020) · Biomicrofluidics · doi:10.1063/1.5133970 · Cited by 30 · see citing works
Trends in Bone Metastasis Modeling
Laranga, R., Duchi, S., Ibrahim, T., Guerrieri, A. N., Donati, D. M., & Lucarelli, E. (2020) · Cancers · doi:10.3390/cancers12082315 · Cited by 29 · see citing works
“Furthermore, microfluidic systems have also been studied in detail to better recapitulate the cancer cell–immune cell interactions, with the ultimate aim of increasing knowledge on cancer immunotherapies [125].”
BackgroundMoghaddam, F. D., Anvar, A., Ilkhani, E., Dadgar, D., Rafiee, M., Ranjbaran, N., Mortazavi, P., Ghoreishian, S. M., Huh, Y. S., & Makvandi, P. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02479-4 · Cited by 37 · see citing works
“A primary challenge is the accurate simulation of the intricate interactions within the immune sys-tem which encompasses a variety of cell types, signaling pathways, and inflammatory responses [204].”
Dhiman, N., Shagaghi, N., Bhave, M. R., Sümer, H., Kingshott, P., & Rath, S. N. (2020) · Advanced Biosystems · doi:10.1002/adbi.201900285 · Cited by 28 · see citing works
Designing Hydrogel-Based Bone-On-Chips for Personalized Medicine
Nasello, G., Cóndor, M., Vaughan, T. J., & Schiavi, J. (2021) · Applied Sciences · doi:10.3390/app11104495 · Cited by 28 · see citing works
“Yet, traditional 2D in vitro models are not suitable for long-term studies and may fail in recapitulating a clinically relevant environment due to the absence of all factors present in vivo [9], but their high output and outcome balance this weakness.”
BackgroundIn Vitro Modeling of Tumor–Immune System Interaction
Mengus, C., Muraro, M. G., Mele, V., Amicarella, F., Manfredonia, C., Foglietta, F., Muenst, S. E., Soysal, S. D., Iezzi, G., & Spagnoli, G. C. (2017) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.7b00077 · Cited by 31 · see citing works
Manoharan, T. J. M., Ravi, K., Suresh, A. P., Acharya, A. P., & Nikkhah, M. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202303658 · Cited by 26 · see citing works
Microfluidic Tumor Vasculature Model to Recapitulate an Endothelial Immune Barrier Expressing FasL
Kim, S., Park, J., Kim, J., & Jeon, J. S. (2021) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.0c01542 · Cited by 26 · see citing works
Huang, R., Li, S., Tian, C., et al. (2022) · British Journal of Cancer · doi:10.1038/s41416-022-01896-2 · Cited by 26 · see citing works
“In addition, we applied a set of 3D-culturing chips devised by MIT researchers [50] to the cellular invasion assay.”
MethodEmerging trends in modeling human liver disease in vitro
Underhill, G. H., & Khetani, S. R. (2019) · APL Bioengineering · doi:10.1063/1.5119090 · Cited by 26 · see citing works
Anti-Cancer Drug Screening with Microfluidic Technology
Monjezi, M., Rismanian, M., Jamaati, H., & Kashaninejad, N. (2021) · Applied Sciences · doi:10.3390/app11209418 · Cited by 26 · see citing works
“Microfluidic technology has various potential applications in cancer research, including drug screening, drug discovery, immunotherapy, and clinical oncology [1,2].”
BackgroundRecent advances in microfluidic models for cancer metastasis research
Xu, H. M., Liu, X., & Le, W. (2018) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2018.04.007 · Cited by 25 · see citing works
Miedel, M. T., Gavlock, D. C., Jia, S., Gough, A., Taylor, D. L., & Stern, A. M. (2019) · Scientific Reports · doi:10.1038/s41598-019-44756-5 · Cited by 24 · see citing works
Nuts and Bolts: Microfluidics for the Production of Biomaterials
Fontana, F., Martins, J. P., Torrieri, G., & Santos, H. A. (2019) · Advanced Materials Technologies · doi:10.1002/admt.201800611 · Cited by 24 · see citing works
Beelen, N. A., Aberle, M. R., Bruno, V., Damink, S. W. M. O., Bos, G. M. J., Rensen, S. S., & Wieten, L. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1133796 · Cited by 23 · see citing works
Use and application of organ-on-a-chip platforms in cancer research
Yu, Y., Zhou, T., & Cao, L.-L. (2023) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-023-00790-7 · Cited by 25 · see citing works
“In vitro studies have demonstrated that the production of tumor-associated antigens is decreased in 3D models compared with that in 2D models, and the advantages of 3D models in tumor immunity research are clearly highlighted in microfluidic systems (Boussommier-Calleja et al. 2016).”
BackgroundAlves, C. L., Deng, Z., Kermeci, N., & Shih, S. C. C. (2024) · Lab on a Chip · doi:10.1039/d3lc01090b · Cited by 22 · see citing works
Structural colour enhanced microfluidics
Qin, D., Gibbons, A. H., Ito, M. M. M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29956-4 · Cited by 21 · see citing works
Fan, Y., Xu, C., Deng, N., Gao, Z., Jiang, Z., Li, X., Zhou, Y., Pei, H., Li, L., & Tang, B. (2023) · Lab on a Chip · doi:10.1039/d2lc01077a · Cited by 21 · see citing works
Emerging Strategies in 3D Culture Models for Hematological Cancers
Barozzi, D., & Scielzo, C. (2023) · HemaSphere · doi:10.1097/hs9.0000000000000932 · Cited by 21 · see citing works
Modeling the tumor immune microenvironment for drug discovery using 3D culture
Lee, J. Y., & Chaudhuri, O. (2021) · APL Bioengineering · doi:10.1063/5.0030693 · Cited by 22 · see citing works
- Authors
- Boussommier-Calleja, A., Li, R., Chen, M. B., Wong, S. C., & Kamm, R. D.
- Affiliations
- Massachusetts Institute of Technology (US)
- Agency for Science, Technology and Research (SG)
- Corresponding author
- Kamm, Roger D.
- Venue
- Trends in Cancer
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 2
- Issue
- 1
- Pages
- 6-19
- ISSN
- 2405-8025 (ISSN-L)
- 2405-8033
- PMC
- PMC4743529
- OpenAlex
- W2279226389
- Cited by
- 224
- References
- 127
- Citations by year
- 2026: 11 · 2025: 26 · 2024: 18 · 2023: 24 · 2022: 23 · 2021: 24 · 2020: 34 · 2019: 17 · 2018: 24 · 2017: 16 · 2016: 6 · 2015: 1
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Trends in cancer (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- Cancer Research Institute
- National Cancer Institute (R33CA174550, U01CA202177)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Bio-sensing Technologies
- Keywords
- microfluidics, tumor-immune interactions, tumor microenvironment, immunotherapy, metastasis, tumor-immune cell interactions, 3D cell culture, in vitro model, real-time monitoring, microfluidic assay
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read under definition version 3 (extract-v3) on 2026-09-28.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.
Cited sources are checked by gpt-6-sol.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
