T Cell Surveillance of Oncogene-Induced Prostate Cancer Is Impeded by T Cell-Derived TGF-β1 Cytokine
Open accessAbstract
Tolerance induction in T cells takes place in most tumors and is thought to account for tumor evasion from immune eradication. Production of the cytokine TGF-β is implicated in immunosuppression, but the cellular mechanism by which TGF-β induces T cell dysfunction remains unclear. With a transgenic model of prostate cancer, we showed that tumor development was not suppressed by the adaptive immune system, which was associated with heightened TGF-β signaling in T cells from the tumor-draining lymph nodes. Blockade of TGF-β signaling in T cells enhanced tumor antigen-specific T cell responses and inhibited tumor development. Surprisingly, T cell- but not Treg cell-specific ablation of TGF-β1 was sufficient to augment T cell cytotoxic activity and blocked tumor growth and metastases. These findings reveal that T cell production of TGF-β1 is an essential requirement for tumors to evade immunosurveillance independent of TGF-β produced by tumors.
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Single cell analyses reveal extensive phenotype heterogeneity among Treg cells.
“As single cell analyses reveal extensive phenotype heterogeneity among Treg cells221”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [221]
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References 57 · Cited by 130
- Authors
- Donkor, M. K., Sarkar, A., Savage, P. A., Franklin, R. A., Johnson, L. K., Jungbluth, A. A., Allison, J. P., & Li, M. O.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Ludwig Cancer Research (BE)
- Corresponding author
- Li, Ming O.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 35
- Issue
- 1
- Pages
- 123-134
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC3430371
- OpenAlex
- W2160860231
- Cited by
- 130
- References
- 57
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 7 · 2023: 8 · 2022: 9 · 2021: 16 · 2020: 10 · 2019: 10 · 2018: 4 · 2017: 10 · 2016: 7 · 2015: 5 · 2014: 14 · 2013: 11 · 2012: 6
- FWCI
- 4.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR053595, K01AR053595, R01AR060723, AR060723)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- TGF-β1, prostate cancer, tumor immune evasion, T cell tolerance, T cell dysfunction, T cell cytotoxicity, tumor antigen-specific T cell responses, tumor-draining lymph nodes, metastasis
- MeSH terms
- Adenocarcinoma, Animals, Cytotoxicity, Immunologic, Disease Models, Animal, Humans, Immune Tolerance, Immunologic Surveillance, Lymphocyte Depletion, Male, Mice, Transgenic, Oncogenes, Prostatic Neoplasms, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocyte Subsets, Transforming Growth Factor beta, Tumor Escape, Cell Growth Processes, T-Lymphocytes, Regulatory, Mice
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