The DOI matches its Crossref record; 184 of the 184 references it cites were found in a registry or an index.
Cancer-Associated Fibroblasts and Tumor-Associated Macrophages in Cancer and Cancer Immunotherapy
Open accessAbstract
Our understanding of the tumor microenvironment (TME), including the interplay between tumor cells, stromal cells, immune cells, and extracellular matrix components, is mandatory for the innovation of new therapeutic approaches in cancer. The cell-cell communication within the TME plays a pivotal role in the evolution and progression of cancer. Cancer-associated fibroblasts (CAF) and tumor-associated macrophages (TAM) are major cell populations in the stroma of all solid tumors and often exert protumorigenic functions; however, the origin and precise functions of CAF and TAM are still incompletely understood. CAF and TAM hold significant potential as therapeutic targets to improve outcomes in oncology when combined with existing therapies. The regulation of CAF/TAM communication and/or their differentiation could be of high impact for improving the future targeted treatment strategies. Nevertheless, there is much scope for research and innovation in this field with regards to the development of novel drugs. In this review, we elaborate on the current knowledge on CAF and TAM in cancer and cancer immunotherapy. Additionally, by focusing on their heterogenous functions in different stages and types of cancer, we explore their role as potential therapeutic targets and highlight certain aspects of their functions that need further research.
Overview
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
Figures
![Figure 2 Kaplan–Meier curves depicting overall survival for high and low TAM densities across different cancer types. Overall survival curves, merged data, various cancers. Gastric cancer: Kaplan–Meier overall survival curves for gastric cancer patients with high TAM density (> 671 cells in five 400x microscopic fields; green dotted line) and low density (< 671 cells in five 400x microscopic fields; green solid line). The TAM density in the tumor tissue was negatively associated with overall survival [p=0.0073; (86)]. Breast cancer: Kaplan–Meier curves showing significant correlation (p<0.001) with overall survival according to the numbers of M2 TAM (CD163 high: yellow dotted line; CD163 low: yellow solid line) (87). Multiple myeloma: overall survival outcome based on low and high CD163 TAM (≤ 55 per high power microscopic field; dotted blue line) showing significant survival difference (p<0.001) (88). Ovarian cancer: Kaplan–Meier survival curves comparing high and low M1 (CD80)/M2 (CD163) ratios in patients with ovarian cancer. Patients with an M1/M2 ratio ≥ 1.4 (solid red line) showed a significantly higher overall survival (p=0.02) than those with an M1/M2 ratio < 1.4 (dotted red line) (89).](/paper-figures/cb0d1527c8ae4af3a2882a17d8f82d74/cancer-associated-fibroblasts-and-tumor-associated-macrophages-in-cancer-and-figure-2.jpg)
Verification
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?
The cited source says what the claim attributes to it.
In the citing paper
“Among the various stromal cells within the TME, fibroblasts constitute the dominant cellular mass [27,28,29,30].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [30]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
Macrophage plasticity and polarization: in vivo veritas
Sica, A., & Mantovani, A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59643 · Cited by 6,335
TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells
Mariathasan, S., Turley, S. J., Nickles, D., Castiglioni, A., Yuen, K., Wang, Y., Kadel III, E. E., Koeppen, H., Astarita, J. L., Cubas, R., et al. (2018) · Nature · doi:10.1038/nature25501 · Cited by 5,400
Macrophage Diversity Enhances Tumor Progression and Metastasis
Qian, B., & Pollard, J. W. (2010) · Cell · doi:10.1016/j.cell.2010.03.014 · Cited by 5,349
The consensus molecular subtypes of colorectal cancer
Guinney, J., Dienstmann, R., Wang, X., de Reyniès, A., Schlicker, A., Soneson, C., Marisa, L., Roepman, P., Nyamundanda, G., Angelino, P., et al. (2015) · Nature Medicine · doi:10.1038/nm.3967 · Cited by 5,170
Tumour exosome integrins determine organotropic metastasis
Hoshino, A., Costa-Silva, B., Shen, T.-L., Rodrigues, G., Hashimoto, A., Tesic Mark, M., Molina, H., Kohsaka, S., Di Giannatale, A., Ceder, S., et al. (2015) · Nature · doi:10.1038/nature15756 · Cited by 5,101
Macrophage plasticity, polarization, and function in health and disease
Shapouri‐Moghaddam, A., Mohammadian, S., Vazini, H., Taghadosi, M., Esmaeili, S., Mardani, F., Seifi, B., Mohammadi, A., Afshari, J. T., & Sahebkar, A. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.26429 · Cited by 4,930
Remodelling the extracellular matrix in development and disease
Bonnans, C., Chou, J., & Werb, Z. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3904 · Cited by 4,367
The biology and function of fibroblasts in cancer
Kalluri, R. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.73 · Cited by 4,366
A framework for advancing our understanding of cancer-associated fibroblasts
Sahai, E., Astsaturov, I., Cukierman, E., DeNardo, D. G., Egeblad, M., Evans, R. M., Fearon, D., Greten, F. R., Hingorani, S. R., Hunter, T., et al. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0238-1 · Cited by 3,863 · cited 5×
“Similarly, an initial expansion of local fibroblasts circumscribing early or premalignant lesions in response to tissue neoplasia was observed in mouse models and human tissue studies (14, 28, 29).”
BackgroundInfluential
Cited by
Sorted by citations
Macrophages at the interface of the co-evolving cancer ecosystem
Kloosterman, D. J., & Akkari, L. (2023) · Cell · doi:10.1016/j.cell.2023.02.020 · Cited by 452
Roles of tumor-associated macrophages in anti-PD-1/PD-L1 immunotherapy for solid cancers
Zhang, H., Liu, L., Liu, J., Dang, P., Hu, S., Yuan, W., Sun, Z., Liu, Y., & Wang, C. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01725-x · Cited by 402
Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy
Lu, Q., Kou, D., Lou, S., Ashrafizadeh, M., Aref, A. R., Canadas, I., Tian, Y., Niu, X., Wang, Y., Torabian, P., et al. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01535-8 · Cited by 373
Tumor-associated macrophages: an effective player of the tumor microenvironment
Basak, U., Sarkar, T., Mukherjee, S., Chakraborty, S., Dutta, A., Dutta, S., Nayak, D., Kaushik, S., Das, T., & Sa, G. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1295257 · Cited by 356
Cancer-associated fibroblasts: The chief architect in the tumor microenvironment
Sarkar, M., Nguyen, T., Gundre, E., Ogunlusi, O., El-Sobky, M. H., Giri, B., & Sarkar, T. R. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1089068 · Cited by 150
Metadata
- Authors
- Raskov, H., Orhan, A., Gaggar, S., & Gögenur, I.
- Affiliations
- Zealand University Hospital Køge (DK)
- University of Copenhagen (DK)
- Corresponding author
- Raskov, Hans
- Venue
- Frontiers in Oncology
- Publisher
- Frontiers Media SA
- Published
- 2021-05-20
- Volume
- 11
- Pages
- 668731-668731
- ISSN
- 2234-943X (ISSN-L)
- PMC
- PMC8172975
- OpenAlex
- W3163457197
- Cited by
- 150
- References
- 184
- Citations by year
- 2026: 29 · 2025: 32 · 2024: 37 · 2023: 26 · 2022: 20 · 2021: 6
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Oncology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- cancer-associated fibroblasts, tumor-associated macrophages, tumor microenvironment, cancer immunotherapy, tumor stroma, therapeutic target, intercellular communication, extracellular matrix
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
