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TGFβ shuts the door on T cells

Tobias Bald1, Mark J Smyth2

  • 1Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.

British Journal of Cancer
|June 15, 2018
PubMed

Insights

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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