The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-β signaling in regulatory T cells
Open accessAbstract
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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Cites
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Self-citationRegulatory mechanisms of PD-1/PD-L1 in cancers
Lin, X., Kang, K., Chen, P., Zeng, Z., Li, G., Xiong, W., Yi, M., & Xiang, B. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02023-w · Cited by 784
Energy metabolism in health and diseases
Liu, H., Wang, S., Wang, J., Guo, X., Song, Y., Fu, K., Gao, Z., Liu, D., He, W., & Yang, L.-L. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02141-x · Cited by 399
Lactate: A key regulator of the immune response
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Wei, L., Yang, X., Wang, J., Wang, Z., Wang, Q., Ding, Y., & Yu, A. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02879-7 · Cited by 259
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Metadata
- Authors
- Gu, J., Zhou, J., Chen, Q., Xu, X., Gao, J., Li, X., Shao, Q., Zhou, B., Zhou, H., Wei, S., Wang, Q., Liang, Y., & Lu, L.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2022-06
- Volume
- 39
- Issue
- 12
- Pages
- 110986
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W4283277906
- Cited by
- 490
- References
- 41
- FWCI
- 28.14
- Type
- journal article
- Language
- en
- Open access
- gold
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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., & Lu, L. (2022). Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-β signaling in regulatory T cells. Cell Reports. https://doi.org/10.1016/j.celrep.2022.110986
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
