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TGFβ shuts the door on T cells.
1Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
British Journal of Cancer
|June 15, 2018
Summary
Cancer-associated fibroblasts create a barrier, preventing T cells from attacking tumors. This TGFβ mechanism hinders immunotherapy response in certain cancers.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- T cell exclusion from tumors is a significant challenge in cancer treatment, leading to poor patient outcomes.
- Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment.
- Transforming growth factor beta (TGFβ) is a key signaling molecule implicated in cancer progression.
Discussion:
- Recent research highlights the detrimental role of CAF-derived TGFβ in promoting T cell exclusion in colorectal and urothelial cancers.
- TGFβ signaling by CAFs creates an immunosuppressive environment, preventing anti-tumor T cell infiltration.
- This mechanism may be a significant factor limiting the efficacy of immunotherapies like anti-PD-L1 in specific cancer types.
Key Insights:
- CAF-secreted TGFβ actively excludes T cells from the tumor microenvironment.
- T cell exclusion driven by TGFβ is observed in both colorectal and urothelial cancers.
- In urothelial carcinoma, this exclusion may impair responses to anti-PD-L1 therapy.
Outlook:
- Targeting CAF-derived TGFβ could be a therapeutic strategy to overcome T cell exclusion.
- Understanding this mechanism may improve patient selection for immunotherapy.
- Further research is needed to explore combination therapies involving TGFβ inhibition and immunotherapy.
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