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 - Funding Information:
Acknowledgements We thank members of the M.O.L. laboratory for helpful discussions. This work was supported by a Howard Hughes Medical Institute Faculty Scholar Award (M.O.L.), an award from Mr. William H. and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research and the Center for Experimental Therapeutics at MSKCC (M.O.L.) and a Cancer Center Support Grant (P30 CA08748). B.G.N. and M.H.D. are recipients of F31 CA210332 and F30 AI29273-03 awards from National Institutes of Health. C.C. and S.L. are Cancer Research Institute Irvington Fellows supported by the Cancer Research Institute. E.G.S. is a recipient of a Fellowship from the Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center of MSKCC.
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 - http://www.scopus.com/inward/record.url?scp=85093070338&partnerID=8YFLogxK
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 -