TY - JOUR
T1 - TGF-β suppresses type 2 immunity to cancer
AU - Liu, Ming
AU - Kuo, Fengshen
AU - Capistrano, Kristelle J.
AU - Kang, Davina
AU - Nixon, Briana G.
AU - Shi, Wei
AU - Chou, Chun
AU - Do, Mytrang H.
AU - Stamatiades, Efstathios G.
AU - Gao, Shengyu
AU - Li, Shun
AU - Chen, Yingbei
AU - Hsieh, James J.
AU - Hakimi, A. Ari
AU - Taniuchi, Ichiro
AU - Chan, Timothy A.
AU - Li, Ming O.
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/11/5
Y1 - 2020/11/5
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85093070338
U2 - 10.1038/s41586-020-2836-1
DO - 10.1038/s41586-020-2836-1
M3 - Article
C2 - 33087928
AN - SCOPUS:85093070338
SN - 0028-0836
VL - 587
SP - 115
EP - 120
JO - Nature
JF - Nature
IS - 7832
ER -