TGFβ Suppresses Type 2 Immunity to Cancer

Liu, M.; Kuo, F.; Capistrano, K.; Kang, D.; Nixon, B.; Shi, W.; Chou, C.; Do, M.; Li, S.; Stamatiades, E.; Chen, Y.; Hsieh, J.; Hakimi, A.; Taniuchi, I.; Chan, T.; Li, M.

doi:10.1101/2020.03.04.977629

bioRxiv · 10.1101/2020.03.04.977629

TGFβ Suppresses Type 2 Immunity to Cancer

Liu, M.·Kuo, F.·Capistrano, K.·Kang, D.·Nixon, B.·Shi, W.·Chou, C.·Do, M.·Li, S.·Stamatiades, E.·Chen, Y.·Hsieh, J.·Hakimi, A.·Taniuchi, I.·Chan, T.·Li, M.

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Abstract

The immune system employs two distinct defense strategies against infections: pathogen elimination typified by type 1 immunity, and pathogen containment exemplified by type 2 immunity in association with tissue repair. Akin to infectious diseases, cancer progresses with cancer cell acquisition of microorganism-like behavior propagating at the expense of the host. While immunological mechanisms of cancer cell elimination are well defined, whether immune-mediated cancer cell containment can be induced is poorly understood. Here we show that ablation of transforming growth factor-{beta} receptor II (TGF{beta}RII) in CD4+ T cells promotes tumor tissue healing and halts cancer progression. Notably, the restorative response is dependent on the T helper 2 cytokine IL-4 fortifying vasculature organization that spares only proximal layers of cancer cells from hypoxia, nutrient starvation and death. Thus, type 2 immunity represents an effective cancer defense mechanism, and TGF{beta} signaling in helper T cells may be targeted for novel cancer immunotherapy.

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Liu, M., Kuo, F., Capistrano, K., Kang, D., Nixon, B., Shi, W., Chou, C., Do, M., Li, S., Stamatiades, E., Chen, Y., Hsieh, J., Hakimi, A., Taniuchi, I., Chan, T., Li, M.. 2020-03-05. TGFβ Suppresses Type 2 Immunity to Cancer. https://doi.org/10.1101/2020.03.04.977629

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