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TGF-β suppresses type 2 immunity to cancer

Author

Listed:
  • Ming Liu

    (Memorial Sloan Kettering Cancer Center)

  • Fengshen Kuo

    (Memorial Sloan Kettering Cancer Center)

  • Kristelle J. Capistrano

    (Memorial Sloan Kettering Cancer Center)

  • Davina Kang

    (Memorial Sloan Kettering Cancer Center)

  • Briana G. Nixon

    (Memorial Sloan Kettering Cancer Center
    Cornell University)

  • Wei Shi

    (Memorial Sloan Kettering Cancer Center)

  • Chun Chou

    (Memorial Sloan Kettering Cancer Center)

  • Mytrang H. Do

    (Memorial Sloan Kettering Cancer Center
    Cornell University)

  • Efstathios G. Stamatiades

    (Memorial Sloan Kettering Cancer Center)

  • Shengyu Gao

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Shun Li

    (Memorial Sloan Kettering Cancer Center)

  • Yingbei Chen

    (Memorial Sloan Kettering Cancer Center)

  • James J. Hsieh

    (Washington University)

  • A. Ari Hakimi

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Ichiro Taniuchi

    (RIKEN Center for Integrative Medical Sciences)

  • Timothy A. Chan

    (Memorial Sloan Kettering Cancer Center)

  • Ming O. Li

    (Memorial Sloan Kettering Cancer Center
    Cornell University
    Memorial Sloan Kettering Cancer Center)

Abstract

The immune system uses two distinct defence strategies against infections: microbe-directed pathogen destruction characterized by type 1 immunity1, and host-directed pathogen containment exemplified by type 2 immunity in induction of tissue repair2. Similar to infectious diseases, cancer progresses with self-propagating cancer cells inflicting host-tissue damage. The immunological mechanisms of cancer cell destruction are well defined3–5, but whether immune-mediated cancer cell containment can be induced remains poorly understood. Here we show that depletion of transforming growth factor-β receptor 2 (TGFBR2) in CD4+ T cells, but not CD8+ T cells, halts cancer progression as a result of tissue healing and remodelling of the blood vasculature, causing cancer cell hypoxia and death in distant avascular regions. Notably, the host-directed protective response is dependent on the T helper 2 cytokine interleukin-4 (IL-4), but not the T helper 1 cytokine interferon-γ (IFN-γ). Thus, type 2 immunity can be mobilized as an effective tissue-level defence mechanism against cancer.

Suggested Citation

  • Ming Liu & Fengshen Kuo & Kristelle J. Capistrano & Davina Kang & Briana G. Nixon & Wei Shi & Chun Chou & Mytrang H. Do & Efstathios G. Stamatiades & Shengyu Gao & Shun Li & Yingbei Chen & James J. Hs, 2020. "TGF-β suppresses type 2 immunity to cancer," Nature, Nature, vol. 587(7832), pages 115-120, November.
    • Handle: RePEc:nat:nature:v:587:y:2020:i:7832:d:10.1038_s41586-020-2836-1
    DOI: 10.1038/s41586-020-2836-1
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