Burning lactic acid: a road to revitalizing antitumor immunity

Abstract

Lactic acid (LA) accumulation in tumor microenvironments (TME) has been implicated in immune suppression and tumor progress. Diverse roles of LA have been elucidated, including microenvironmental pH regulation, signal transduction, post-translational modification, and metabolic remodeling. This review summarizes LA functions within TME, focusing on the effects on tumor cells, immune cells, and stromal cells. Reducing LA levels is a potential strategy to attack cancer, which inevitably affects the physiological functions of normal tissues. Alternatively, transporting LA into the mitochondria as an energy source for immune cells is intriguing. We underscore the significance of LA in both tumor biology and immunology, proposing the burning of LA as a potential therapeutic approach to enhance antitumor immune responses.

Keywords

lactic acid / metabolism / tumor immunotherapy

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Nos. 82388201 to B.H., 32090053, 32394003 to J.W.M.), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (No. 2021-I2M-1-021 to B.H.), the Young Top-notch Talent Cultivation Program of Hubei Province (J.W.M.).

Compliance with ethics guidelines

Conflict of interest Jingwei Ma, Liang Tang, Jingxuan Xiao, Ke Tang, Huafeng Zhang, and Bo Huang declare that they have no conflict of interest.

This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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