The DOI matches its Crossref record; 121 of the 127 references it cites were found in a registry or an index; 35 of the 64 sources its claims cite were checked for support.
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.
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Claims the paper makes
20 Own interpretation · 12 No full text of the sources · 11 Partly supported · 6 Supported · 3 Supported so far · 2 Couldn’t confirm · 1 No basis given · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Furthermore, cancer cells promoted macrophage proliferation[64].”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidics: modeling immune-cancer cell interactions
What the sources say
- Partly supportedcites [64] sourceExperimental — accuracy not yet measured
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)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Recently, immunotherapies have shown promising results for reducing metastasis in melanoma or kidney cancer patients[1, 2].”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidic models: developing immunotherapies against metastasis
What the sources say
- Supportedcites [1] source
The opening section describes immunotherapy as producing durable, sometimes complete tumor regression in patients with metastatic melanoma and kidney cancer. This supports the citing sentence’s broad characterization of promising results for reducing metastatic disease. (LLM, conf=0.90)
- Partly supportedcites [2] sourceExperimental — accuracy not yet measured
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)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“They also showed that macrophages in co-culture expressed more Arginine-1, in an analogous manner to macrophage activation in the tumor microenvironment.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidics: modeling immune-cancer cell interactions
What the sources say
- Could not verifycites [48] sourceExperimental — accuracy not yet measured
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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Could not verify
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“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.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidics: modeling immune-cancer cell interactions
What the sources say
- Not checked — no full text of the sourcecites [54] source
- Supportedcites [55] source
The Introduction reports that CD8+ T cells maintained dormancy of disseminated melanoma cells in visceral organs in the mouse model, and that depleting them accelerated tumor outgrowth. This supports the claim that immune cells can attenuate metastasis. (LLM, conf=0.94)
- Supportedcites [56] source
The paper reports that natural killer cells can inhibit metastasis in mice. In the passage labeled Abstract, mice receiving Cbl-b-deficient NK cells had fewer lung melanoma metastases, and the authors conclude that those NK cells inhibit the progression of lung and distant metastases. (LLM, conf=0.93)
- Supportedcites [57] source
The Results section, “Tumor entrained neutrophils inhibit seeding in the pre-metastatic lung” (page unavailable), reports that depleting neutrophils increased metastatic burden and produced about three times as many lung metastatic events in tumor-bearing mice. This supports the claim that immune cells can attenuate metastasis, specifically tumor-entrained neutrophils in this model. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [58]
- Supportedcites [59] source
The paper reports that anti-CD47 treatment increased macrophage phagocytosis of leiomyosarcoma cells, and the neoadjuvant-treatment results report that it almost completely inhibited lung metastases in mice. This supports the broad claim that immune cells can help attenuate metastasis, in the context of antibody treatment in a mouse model. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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].”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidic: modeling the metastatic cascade
What the sources say
- Supportedcites [29] source
Citation [29] is attached to the claim that cancer cells communicate with their microenvironment, not to the later claims about organ-specific cells or organ-selectivity. The passage on paracrine signalling loops between cancer cells, macrophages and endothelial cells supports that claim (passage [4]; page not provided). (LLM, conf=0.91)
- Partly supportedcites [30] sourceExperimental — accuracy not yet measured
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)
- Not checked — no full text of the sourcecites [31] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“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.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidic: modeling the metastatic cascade
What the sources say
- Supportedcites [24] source
The Introduction identifies endothelial-derived thrombospondin-1 as a tumor suppressor, and the Results report that endothelial cells induced sustained quiescence in breast cancer cells. The Discussion specifies that stable microvasculature induces this quiescence via thrombospondin-1. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“One of the major current limitations of in vitro metastatic models is their lack of organ-specificity[28].”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidic: modeling the metastatic cascade
What the sources say
- Supportedcites [28] source
In “Cancer cell odyssey in the metastatic cascade,” the paper calls the lack of organ-specific in vitro models a significant limitation of current systems. The “Microfluidic tools for in vitro cancer models” section likewise says that the extravasation assays discussed lack organ specificity. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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].”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidic: modeling the metastatic cascade
What the sources say
- Partly supportedcites [21] sourceExperimental — accuracy not yet measured
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)
- Partly supportedcites [23] sourceExperimental — accuracy not yet measured
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)
- Partly supportedcites [24] sourceExperimental — accuracy not yet measured
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)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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).”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidic: modeling the metastatic cascade
What the sources say
- Not checked — no full text of the sourcecites [13] source
- Not checked — no full text of the sourcecites [14] source
- Partly supportedcites [15] sourceExperimental — accuracy not yet measured
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)
- Not checked — no full text of the sourcecites [16] source
- Not checked — no full text of the sourcecites [17] source
- Supportedcites [18] sourceExperimental — accuracy not yet measured
The citation is attached to intravasation, not to the sentence’s examples of EMT, adhesion, or extravasation. The Results section describes a 3D microfluidic assay with an endothelial monolayer that permits observation of tumor-cell intravasation. (LLM, conf=0.94)
- Supportedcites [19] sourceExperimental — accuracy not yet measured
The citation to this paper is attached to intravasation, not to EMT, adhesion, or extravasation. The Metastasis chip design and Discussion sections describe a microfluidic assay that models cancer-cell intravasation into engineered microvessels. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidics: modeling immune-cancer cell interactions
What the sources say
- Partly supportedcites [50] sourceExperimental — accuracy not yet measured
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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
- Borderline: one of the tests for a substantial claim is unclear. 1
- It may state two separate claims as one. 16
- Probably not a substantial claim. 8
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“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.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidics: modeling immune-cancer cell interactions
What the sources say
- Supportedcites [48] source
The Abstract reports that only wild-type spleen cells established physical interactions with melanoma cells, while IRF-8 knockout cells showed poor reactivity. The Results (‘Making up the experiment for data-drive’) likewise report migration and clustering toward melanoma cells for wild-type cells, but no focused response by knockout cells. Page numbers are not provided in our copy. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [49] source
- Supportedcites [50] source
The Discussion reports that WT splenocytes crossed the microchannels toward the melanoma compartment, while IRF-8 KO cells were unable to move forward. The section on splenocyte migration also reports longer-lasting contact with melanoma cells for WT than IRF-8 KO splenocytes. The finding is supported in the paper’s B16.F10 melanoma microfluidic model. (LLM, conf=0.94)
direct- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Borderline substantial claim. It is unclear whether the paper’s conclusions depend on it. It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“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].”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidics: modeling immune-cancer cell interactions
What the sources say
- Supportedcites [37] source
The Abstract says the tumour microenvironment polarizes recruited macrophages into ‘tumour-educated’ cells that promote tumour progression and metastasis. The Immune escape section describes how tumours alter immune-cell functions to avoid immune rejection, supporting the claim about tolerance in substance. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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].”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidic: modeling the metastatic cascade
What the sources say
- Partly supportedcites [21] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Microfluidic: modeling the metastatic cascade · plain
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“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.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidic: modeling the metastatic cascade
What the sources say
- Not checked — no full text of the sourcecites [6] source
- Could not verifycites [7] sourceExperimental — accuracy not yet measured
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)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“For example, neutrophils are known to assist with tumor cell extravasation following platelet aggregation around the tumor cell[60, 61].”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidics: modeling immune-cancer cell interactions
What the sources say
- Not checked — no full text of the sourcecites [60] source
- Partly supportedcites [61] sourceExperimental — accuracy not yet measured
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)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Every source the paper cites for this claim was checked and supports it.
In the paper
“PDMS can also adsorb small hydrophobic molecules[9], which can be problematic for drug screening studies.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidic vs. traditional models for cancer and metastasis research
What the sources say
- Supportedcites [9] source
The citation is attached to the claim that PDMS takes up small hydrophobic molecules. The Introduction (Hydrophobic absorption; page unavailable) describes their partitioning into PDMS, and the Discussion (page unavailable) reports a substantial reduction in medium estrogen. The paper calls this absorption into the polymer bulk rather than surface adsorption. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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].”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Concluding Remarks
What the sources say
- Not checked — no full text of the sourcecites [60] source
- Partly supportedcites [61] sourceExperimental — accuracy not yet measured
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)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidics: modeling immune-cancer cell interactions
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidic: modeling the metastatic cascade
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidics: modeling immune-cancer cell interactions
What the sources say
- Not checked — no full text of the sourcecites [51] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Uniquely, the presence of microfluidic channels permits precise control of flow, allowing the study of many important biomechanical processes such as shear stress.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidic vs. traditional models for cancer and metastasis research
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“For example, retrieving cells from microfluidic devices for subsequent biochemical studies is possible but not straightforward [6].”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidic vs. traditional models for cancer and metastasis research
What the sources say
- Not checked — no full text of the sourcecites [6] source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidic models: developing immunotherapies against metastasis
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidics: modeling immune-cancer cell interactions
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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].”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Microfluidics: modeling immune-cancer cell interactions
What the sources say
- Not checked — no full text of the sourcecites [47] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Microfluidic systems offer the potential for high throughput, quantitative clinical analyses.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Outlook for future microfluidic applications in immunotherapy
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Outlook for future microfluidic applications in immunotherapy
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Concluding Remarks
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Outlook for future microfluidic applications in immunotherapy
What the sources say
- Not checked — no full text of the sourcecites [86] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eventually, microfluidic systems could represent an important intermediate step, bridging current in vitro high throughput screens and animal studies and human clinical trials.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Concluding Remarks
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Despite their tremendous experimental potential, to date, microfluidic studies have not been widely exploited to study cancer/immune cell interactions.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Outlook for future microfluidic applications in immunotherapy
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Concluding Remarks
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
In the paper
“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].”
§ Microfluidics: A new tool for modeling cancer-immune interactions > Outlook for future microfluidic applications in immunotherapy
What the sources say
- Not checked — no full text of the sourcecites [84] source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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.”
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BackgroundInfluentialThe perivascular niche regulates breast tumour dormancy
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“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].”
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 1,089
Macrophage Regulation of Tumor Responses to Anticancer Therapies
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“enhance or hinder) tumor responses to traditional anti-cancer therapies[41, 42].”
BackgroundThree-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function
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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×
“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
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BackgroundBiological implications of polydimethylsiloxane-based microfluidic cell culture
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“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].”
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Platelets guide the formation of early metastatic niches
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BackgroundEngineered In Vitro Disease Models
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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×
“enhance or hinder) tumor responses to traditional anti-cancer therapies[41, 42].”
BackgroundInterstitial flow influences direction of tumor cell migration through competing mechanisms
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“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
The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells
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Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1
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“cytokine profiling, transcriptomics and proteomics of immune cells[76] [77]) to diagnose and tailor drug treatment[65], as reviewed elsewhere[45].”
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Invadopodia Are Required for Cancer Cell Extravasation and Are a Therapeutic Target for Metastasis
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Engineering microscale cellular niches for three-dimensional multicellular co-cultures
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“Furthermore, cancer cells promoted macrophage proliferation[64].”
Biological applications of microfluidic gradient devices
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“, cytokines) complex gradients in the microfluidic assay in a more precise and sustained manner than in macro-scale in vitro systems[5].”
BackgroundIn vitro three‐dimensional (3D) models in cancer research: An update
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Microfluidic Endothelium for Studying the Intravascular Adhesion of Metastatic Breast Cancer Cells
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Mechanisms of tumor cell extravasation in an in vitro microvascular network platform
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“In addition, μVNs replicate better the 3D vessel architecture and endothelial barrier function [21].”
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Apoptosis: an early event in metastatic inefficiency.
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“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×
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BackgroundSelf-citationChemokines: role in inflammation and immune surveillance
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“For example, immune cells infiltrating tissues are recruited from the bloodstream by inflammatory chemokine/cytokine gradients[43].”
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“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].”
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“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 215 · cited 1×
“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., Balci, 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 210
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×
“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
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Lessons from patient-derived xenografts for better in vitro modeling of human cancer
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‘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×
“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…”
MethodLiu, S., & Leach, S. D. (2011) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130330 · Cited by 180
Chip in a lab: microfluidics for next generation life science research
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“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.”
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Cross talk between cancer and immune cells: exploring complex dynamics in a microfluidic environment
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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 158 · cited 1×
“cytokine profiling, transcriptomics and proteomics of immune cells[76] [77]) to diagnose and tailor drug treatment[65], as reviewed elsewhere[45].”
BackgroundA 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×
“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×
“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×
“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 138 · cited 1×
“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×
“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
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 124
Pisano, M., Triacca, V., Barbee, K. A., & Swartz, M. A. (2015) · Integrative Biology · doi:10.1039/c5ib00085h · Cited by 112
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
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×
“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
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 103 · cited 1×
“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 100 · cited 1×
“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
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
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×
“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
Nesmith, A. P., Agarwal, A., McCain, M. L., & Parker, K. K. (2014) · Lab on a Chip · doi:10.1039/c4lc00688g · Cited by 94
“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 93 · cited 3×
“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].”
BackgroundCancer-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×
“They observed the migration of macrophages towards cancer cells [48] and tested different chemotherapy treatments in the microfluidic device.”
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
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×
“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×
“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×
“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
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×
“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
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
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×
“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
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×
“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×
“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].”
BackgroundMattei, 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×
“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.”
MethodA 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 56
Kim, 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
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
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×
“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×
“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×
“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
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
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×
“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×
“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×
“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×
“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
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×
“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×
“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
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 612
Hoarau-Véchot, J., Rafii, A., Touboul, C., & Pasquier, J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19010181 · Cited by 489
“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 320
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 286
“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
“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].”
Background
Metadata
- 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
- 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
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