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Cited by 806T-cell and B-cell ImmunologyCancer Immunotherapy and BiomarkersImmunotherapy and Immune Responses

Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-β signals in vivo

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Chen, Mei-Ling, Pittet, Mikaël J., Gorelik, Leonid, Flavell, Richard A., Weissleder, Ralph, von Boehmer, Harald, Khazaie, Khashayarsha·2005·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0408197102PMC PMC544311
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Abstract

Cancer patients can harbor significant numbers of CD8 and CD4 T cells with specificities to tumor antigens (Ags). Yet, in most cases, such T cells fail to eradicate the tumor in vivo. Here, we investigated the interference of Ag-specific CD4 + CD25 + regulatory T cells (Treg) with the tumor-specific CD8 T cell immune response in vivo , by monitoring the homing, expansion, and effector function of both subsets in draining and nondraining lymph nodes. The results show that CD8 cells expand to the same extent and produce similar levels of IFN-γ in the presence or absence of Ag-specific Treg. Nevertheless, these Treg abrogate CD8 T cell-mediated tumor rejection by specifically suppressing the cytotoxicity of expanded CD8 cells. The molecular mechanism of suppression involves TGF-β because expression of a dominant-negative TGF-β receptor by tumor-specific CD8 cells renders them resistant to suppression and is associated with tumor rejection and unimpaired cytotoxicity.

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  • Treg cells contribute to macrophage and neutrophil polarization towards a regenerative rather than inflammatory cell state.

    “and contribute to macrophage and neutrophil polarization towards a regenerative rather than inflammatory cell state58,63,82,145,172,173,218,219.”

    From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [58]

  • Treg cells functionally repress the tumor-killing activity of CD8+ T cells through various activities, including TGF-β1 activation.

    “These then functionally repress, through various activities, including TGF-β1 activation82,145, the tumor-killing activity of CD8+ T cells 58,63,82,145,218,219”

    From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [58]

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Authors
Chen, M.-L., Pittet, M. J., Gorelik, L., Flavell, R. A., Weissleder, R., von Boehmer, H., & Khazaie, K.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Biogen (United States) (US)
  • Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115; Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129; and Section of Immunobiology, School of Medicine, and Howard Hughes Medical Institute, Yale University, New Haven, CT 06520
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2004-12-27
Volume
102
Issue
2
Pages
419-424
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0408197102
PMC
PMC544311
OpenAlex
W2093608608
Cited by
806
References
42
Citations by year
2026: 12 · 2025: 31 · 2024: 30 · 2023: 29 · 2022: 38 · 2021: 46 · 2020: 36 · 2019: 37 · 2018: 28 · 2017: 28 · 2016: 38 · 2015: 31 · 2014: 29 · 2013: 27 · 2012: 35
FWCI
17.50
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders
National Cancer Institute (R33 CA97728-02, F33CA097728)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
regulatory T cells, CD8+ T cells, TGF-beta signaling, tumor rejection, interferon-gamma, T cell homing, draining lymph nodes, tumor immunosuppression, CD4+CD25+ T cells
MeSH terms
Animals, Cell Differentiation, Cell Movement, Cytotoxicity, Immunologic, Interferon-gamma, Mice, Inbred BALB C, Tumor Necrosis Factor-alpha, Transforming Growth Factor beta, CD8-Positive T-Lymphocytes, T-Lymphocytes, Regulatory, Mice

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