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TGF-β suppresses type 2 immunity to cancer

Ming Liu1, Fengshen Kuo2, Kristelle J Capistrano1

  • 1Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Nature
|October 22, 2020
PubMed

Insights

Type 2 immunity, typically for tissue repair, can fight cancer. Depleting TGFBR2 in CD4+ T cells triggers this response, halting tumor growth through vascular remodeling and hypoxia.

Area of Science:

  • Immunology
  • Oncology
  • Tissue Repair

Background:

  • The immune system employs type 1 immunity for pathogen destruction and type 2 immunity for tissue repair.
  • While cancer cell destruction by immunity is understood, immune-mediated cancer cell containment is less clear.

Purpose of the Study:

  • To investigate if type 2 immunity can be harnessed for immune-mediated cancer cell containment.
  • To explore the role of transforming growth factor-β receptor 2 (TGFBR2) in CD4+ T cells in cancer progression.

Main Methods:

  • Depletion of TGFBR2 in CD4+ T cells in a cancer model.
  • Analysis of immune responses, tissue healing, and vascular remodeling.
  • Assessment of cancer cell hypoxia and survival.

Main Results:

  • Depletion of TGFBR2 in CD4+ T cells, but not CD8+ T cells, halted cancer progression.
  • This halt was mediated by tissue healing and blood vessel remodeling, leading to cancer cell hypoxia.
  • The protective response relied on the T helper 2 cytokine interleukin-4 (IL-4), not T helper 1 cytokine interferon-γ (IFN-γ).

Conclusions:

  • Type 2 immunity can serve as a tissue-level defense mechanism against cancer.
  • Targeting TGFBR2 in CD4+ T cells can induce a host-directed, tissue-healing response to control cancer.

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