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Cited by 940TGF-β signaling in diseasesImmune cells in cancerT-cell and B-cell Immunology

The polarization of immune cells in the tumour environment by TGFβ

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Flavell, Richard A., Sanjabi, Shomyseh, Wrzesinski, Stephen H., Licona-Limón, Paula·2010·Nature Reviews Immunology
DOI 10.1038/nri2808PMC PMC3885992
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Abstract

Transforming growth factor-beta (TGFbeta) is an immunosuppressive cytokine produced by tumour cells and immune cells that can polarize many components of the immune system. This Review covers the effects of TGFbeta on natural killer (NK) cells, dendritic cells, macrophages, neutrophils, CD8(+) and CD4(+) effector and regulatory T cells, and NKT cells in animal tumour models and in patients with cancer. Collectively, many recent studies favour the hypothesis that blocking TGFbeta-induced signalling in the tumour microenvironment enhances antitumour immunity and may be beneficial for cancer therapy. An overview of the current drugs and reagents available for inhibiting TGFbeta-induced signalling and their phase in clinical development is also provided.

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  • CAFs secrete growth factors, proinflammatory cytokines, and chemokines, particularly TGF-β, IL-6, and CCL2, which recruit immunosuppressive cells into the tumor stroma and lead to immune escape.

    “In addition, CAFs secrete substantial amounts of growth factors, proinflammatory cytokines, and chemokines, particularly TGF-β, IL-6, and CC-chemokine ligand 2, which recruit immunosuppressive cells into the tumor stroma and lead to immune escape 20-22.”

    From TBX3 shapes an immunosuppressive microenvironment and induces immunotherapy resistance (2025) · cites this paper as [20]

    The section on TGFβ’s effects on innate immune cells (page unavailable) says TGFβ-mediated macrophage recruitment into skin tumours has an important role in immune escape. But the paper does not identify CAFs as the source of those signals or support the claimed secretion and recruitment roles of IL-6 and CCL2; its discussion of regulatory-cell trafficking instead mentions CCL22 produced by tumour-associated macrophages. (LLM, conf=0.87)

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Cited by

Sorted by citations

Authors
Flavell, R. A., Sanjabi, S., Wrzesinski, S. H., & Licona-Limón, P.
Affiliations
  • Yale University (US)
  • University of California, San Francisco (US)
Corresponding author
Flavell, Richard A.
ORCID
Venue
Nature Reviews Immunology
Publisher
Springer Science and Business Media LLC
Published
2010-07-09
Volume
10
Issue
8
Pages
554-567
ISSN
  • 1474-1733 (ISSN-L)
  • 1474-1741
DOI
10.1038/nri2808
PMC
PMC3885992
OpenAlex
W2020914260
Cited by
940
References
5
Citations by year
2026: 32 · 2025: 51 · 2024: 48 · 2023: 70 · 2022: 75 · 2021: 79 · 2020: 68 · 2019: 56 · 2018: 54 · 2017: 62 · 2016: 47 · 2015: 69 · 2014: 50 · 2013: 56 · 2012: 59
FWCI
4.97
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature reviews. Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Cancer Institute (CA121974, P50CA121974)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK051665, R01DK051665)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
TGF-beta, tumor microenvironment, immune cell polarization, immunosuppression, antitumor immunity, natural killer cells, dendritic cells, tumour-associated macrophages, neutrophils, regulatory T cells, CD8+ T cells, CD4+ T cells, NKT cells, cancer immunotherapy
MeSH terms
Animals, Antineoplastic Agents, Dendritic Cells, Hematopoiesis, Extramedullary, Humans, Immunosuppression Therapy, Killer Cells, Natural, Macrophages, Neoplasms, Neutrophils, Signal Transduction, T-Lymphocyte Subsets, Cytokines, Transforming Growth Factor beta, Cell Polarity, T-Lymphocytes, Regulatory

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