Dissecting effects of anti-cancer drugs and cancer-associated fibroblasts by on-chip reconstitution of immunocompetent tumor microenvironments
Open accessAbstract
A major challenge in cancer research is the complexity of the tumor microenvironment, which includes the host immunological setting. Inspired by the emerging technology of organ-on-chip, we achieved 3D co-cultures in microfluidic devices (integrating four cell populations: cancer, immune, endothelial, and fibroblasts) to reconstitute ex vivo a human tumor ecosystem (HER2 + breast cancer). We visualized and quantified the complex dynamics of this tumor-on-chip, in the absence or in the presence of the drug trastuzumab (Herceptin), a targeted antibody therapy directed against the HER2 receptor. We uncovered the capacity of the drug trastuzumab to specifically promote long cancer-immune interactions (>50 min), recapitulating an anti-tumoral ADCC (antibody-dependent cell-mediated cytotoxicity) immune response. Cancer-associated fibroblasts (CAFs) antagonized the effects of trastuzumab. These observations constitute a proof of concept that tumors-on-chip are powerful platforms to study ex vivo immunocompetent tumor microenvironments, to characterize ecosystem-level drug responses, and to dissect the roles of stromal components.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Factors in the tumor microenvironment, such as cancer-associated fibroblasts, can suppress the immune system.
“Also, factors in the TME, such as CAFs, can suppress the immune system.”
From Cancer-on-chip models for metastasis: importance of the tumor microenvironment (2024) · cites this paper as [111]
In a breast cancer-on-chip model, presence of cancer-associated fibroblasts inhibited the antitumor effect of the Her2 receptor-blocking antibody trastuzumab by preventing long cancer-immune cell interactions.
“In a breast CoC model, presence of CAFs inhibited the antitumor effect of the Her2 receptor-blocking antibody trastuzumab by preventing long cancer-immune cell interactions [111].”
From Cancer-on-chip models for metastasis: importance of the tumor microenvironment (2024) · cites this paper as [111]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 46 · Cited by 184
- Authors
- Nguyen, M., De Ninno, A., Mencattini, A., Mermet-Meillon, F., Fornabaio, G., Evans, S. S., Cossutta, M., Khira, Y., Han, W., Sirven, P., Pelon, F., Di Giuseppe, D., Bertani, F. R., Gerardino, A., Yamada, A., Descroix, S., Soumelis, V., Mechta-Grigoriou, F., Zalcman, G., Camonis, J., Martinelli, E., Businaro, L., & Parrini, M. C.
- Affiliations
- University of Rome Tor Vergata (IT)
- Inserm (FR)
- National Research Council (IT)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Parrini, Maria Carla
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 25
- Issue
- 13
- Pages
- 3884-3893.e3
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2906206485
- Cited by
- 184
- References
- 46
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 29 · 2023: 37 · 2022: 30 · 2021: 32 · 2020: 16 · 2019: 5
- FWCI
- 5.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ligue Contre le Cancer (RS14/75-54)
- Institut National Du Cancer
- Institut Curie
- Institut National de la Santé et de la Recherche Médicale (EQ2016-01)
- Fondation pour la Recherche Médicale (DGE20111123020, ING20160435436)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Keywords
- tumor microenvironment, cancer-associated fibroblasts, trastuzumab, HER2-positive breast cancer, tumor-on-a-chip, microfluidic co-culture, antibody-dependent cellular cytotoxicity, tumor-immune interactions, anticancer drug response, stromal components, organ-on-a-chip
- MeSH terms
- Trastuzumab, Cancer-Associated Fibroblasts, Animals, Antineoplastic Agents, Cattle, Cell Communication, Humans, Immunocompetence, Neoplasm Invasiveness, Stromal Cells, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, Cell Line, Tumor, Tumor Microenvironment, Human Umbilical Vein Endothelial Cells
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.
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
