ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Cell-intrinsic abrogation of TGF-β signaling delays but does not prevent dysfunction of self/tumor-specific CD8 T cells in a murine model of autochthonous prostate cancer.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- TGFβ control of immune responses in cancer: a holistic immuno-oncology perspective.Nature reviews. Immunology · 2023Review
- Precision oncology for breast cancer through clinical trials.Clinical & experimental metastasis · 2022Review
- Combined targeting of soluble latent TGF-ß and a solid tumor-associated antigen with adapter CAR T cells.Oncoimmunology · 2022Article
- Emerging Approaches for Solid Tumor Treatment Using CAR-T Cell Therapy.International journal of molecular sciences · 2021Review
- TGFβ1: An Indicator for Tumor Immune Microenvironment of Colon Cancer From a Comprehensive Analysis of TCGA.Frontiers in genetics · 2021Article
- Tumor-reprogrammed resident T cells resist radiation to control tumors.Nature communications · 2019Article
- 3D models in the new era of immune oncology: focus on T cells, CAF and ECM.Journal of experimental & clinical cancer research : CR · 2019Review
- Review
- Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies.Cancer cell · 2017Review
- Dysregulation of TGFβ1 Activity in Cancer and Its Influence on the Quality of Anti-Tumor Immunity.Journal of clinical medicine · 2016Review
- New Strategies in Engineering T-cell Receptor Gene-Modified T cells to More Effectively Target Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Review
- T Cells Engineered against a Native Antigen Can Surmount Immunologic and Physical Barriers to Treat Pancreatic Ductal Adenocarcinoma.Cancer cell · 2015Article
- Whole-body irradiation increases the magnitude and persistence of adoptively transferred T cells associated with tumor regression in a mouse model of prostate cancer.Cancer immunology research · 2014Article
- Enhancement of the T-cell armamentarium as a cell-based therapy for prostate cancer.Cancer research · 2014Article
- Re-adapting T cells for cancer therapy: from mouse models to clinical trials.Immunological reviews · 2014Review
- TGF-β: guardian of T cell function.Journal of immunology (Baltimore, Md. : 1950) · 2013Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Adoptive T cell therapy (ACT) for the treatment of established cancers is actively being pursued in clinical trials. However, poor in vivo persistence and maintenance of antitumor activity of transferred T cells remain major problems. TGF-β is a potent immunosuppressive cytokine that is often expressed at high levels within the tumor microenvironment, potentially limiting T cell-mediated antitumor activity. In this study, we used a model of autochthonous murine prostate cancer to evaluate the effect of cell-intrinsic abrogation of TGF-β signaling in self/tumor-specific CD8 T cells used in ACT to target the tumor in situ. We found that persistence and antitumor activity of adoptively transferred effector T cells deficient in TGF-β signaling were significantly improved in the cancerous prostate. However, over time, despite persistence in peripheral lymphoid organs, the numbers of transferred cells in the prostate decreased and the residual prostate-infiltrating T cells were no longer functional. These findings reveal that TGF-β negatively regulates the accumulation and effector function of transferred self/tumor-specific CD8 T cells and highlight that, when targeting a tumor Ag that is also expressed as a self-protein, additional substantive obstacles are operative within the tumor microenvironment, potentially hampering the success of ACT for solid tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.