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Jian Gu, Jinren Zhou, Qiuyang Chen, Xiaozhang Xu, Ji Gao, Xiangyu Li, Qing Shao, Bo Zhou, Haoming Zhou, Song Wei and 3 more
Regulatory T (Treg) cells play a vital role in maintaining the immunosuppressive tumor microenvironment. Lactate is a crucial metabolite in cancer and is related to tumor prognosis, metastasis, and overall survival. In this study, we focus on the effects of lactate on Treg cells. In vitro, lactate improves Treg cell stability and function, whereas lactate degradation reduces Treg cell induction, increases antitumor immunity, and decreases tumor growth in mice. Mechanistically, lactate modulates Treg cell generation through lactylation of Lys72 in MOESIN, which improves MOESIN interaction with transforming growth factor β (TGF-β) receptor I and downstream SMAD3 signaling. Cotreatment with anti-PD-1 and a lactate dehydrogenase inhibitor has a stronger antitumor effect than anti-PD-1 alone. Individuals with hepatocellular carcinoma who responded to anti-PD-1 treatment have lower levels of MOESIN lactylation in Treg cells than nonresponding individuals. Thus, we identify lactate as an essential small molecule that reinforces Treg cells in the tumor microenvironment through lactylation.
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Gu, J., Zhou, J., Chen, Q., Xu, X., Gao, J., Li, X., Shao, Q., Zhou, B., Zhou, H., Wei, S., Wang, Q., Liang, Y., & Lü, L. (2022). Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-β signaling in regulatory T cells. Cell Reports, 39(12), 110986. https://doi.org/10.1016/j.celrep.2022.110986
Gu, Jian, et al. "Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-β signaling in regulatory T cells." Cell Reports, vol. 39, no. 12, 2022, pp. 110986, https://doi.org/10.1016/j.celrep.2022.110986.
Gu, Jian, Jinren Zhou, Qiuyang Chen, Xiaozhang Xu, Ji Gao, Xiangyu Li, Qing Shao, et al. "Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-β signaling in regulatory T cells." Cell Reports 39, no. 12 (2022): 110986. https://doi.org/10.1016/j.celrep.2022.110986.
Gu J., Zhou J., Chen Q. [и др.] Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-β signaling in regulatory T cells // Cell Reports. — 2022. — Vol. 39, № 12. — P. 110986. — URL: https://doi.org/10.1016/j.celrep.2022.110986
@article{gu2022tumor,
title = {{Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-β signaling in regulatory T cells}},
author = {Jian Gu and Jinren Zhou and Qiuyang Chen and Xiaozhang Xu and Ji Gao and Xiangyu Li and Qing Shao and Bo Zhou and Haoming Zhou and Song Wei and Qi Wang and Yuan Liang and Ling Lü},
journal = {Cell Reports},
year = {2022},
volume = {39},
number = {12},
pages = {110986},
doi = {10.1016/j.celrep.2022.110986},
url = {https://doi.org/10.1016/j.celrep.2022.110986}
}TY - JOUR AU - Gu, Jian AU - Zhou, Jinren AU - Chen, Qiuyang AU - Xu, Xiaozhang AU - Gao, Ji AU - Li, Xiangyu AU - Shao, Qing AU - Zhou, Bo AU - Zhou, Haoming AU - Wei, Song AU - Wang, Qi AU - Liang, Yuan AU - Lü, Ling TI - Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-β signaling in regulatory T cells JO - Cell Reports VL - 39 IS - 12 SP - 110986 PY - 2022 DA - 2022/06/01 DO - 10.1016/j.celrep.2022.110986 UR - https://doi.org/10.1016/j.celrep.2022.110986 ER -
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