TGF-β suppresses type 2 immunity to cancer

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. Hsieh, A. Ari Hakimi, Ichiro Taniuchi, Timothy A. Chan, Ming O. Li

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

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.

Original languageEnglish
Pages (from-to)115-120
Number of pages6
JournalNature
Volume587
Issue number7832
DOIs
StatePublished - Nov 5 2020

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