Open AccessTGF-β suppresses type 2 immunity to cancer
Author(s) -
Ming Liu,
Fengshen Kuo,
Kristelle J. Capistrano,
Davina Kang,
Briana G. Nixon,
Shi Wei,
Chun Chou,
H. Mytrang,
Efstathios G. Stamatiades,
Shengyu Gao,
Shun Li,
Yingbei Chen,
James J. Hsieh,
A. Ari Hakimi,
Ichiro Taniuchi,
Timothy A. Chan,
Ming O. Li
Publication year - 2020
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/s41586-020-2836-1
Subject(s) - immune system , immunity , immunology , biology , cytokine , cancer , cancer cell , transforming growth factor , cd8 , cancer research , microbiology and biotechnology , genetics
The immune system uses two distinct defence strategies against infections: microbe-directed pathogen destruction characterized by type 1 immunity 1 , and host-directed pathogen containment exemplified by type 2 immunity in induction of tissue repair 2 . Similar to infectious diseases, cancer progresses with self-propagating cancer cells inflicting host-tissue damage. The immunological mechanisms of cancer cell destruction are well defined 3-5 , 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.