Dual impacts of serine/glycine-free diet in enhancing antitumor immunity and promoting evasion via PD-L1 lactylation

The effect of the serine/glycine-free diet (-SG diet) on colorectal cancer (CRC) remains unclear; meanwhile, programmed death-1 (PD-1) inhibitors are less effective for most CRC patients. Here, we demonstrate that the -SG diet inhibits CRC growth and promotes the accumulation of cytotoxic T cells to enhance antitumor immunity. Additionally, we also identified the lactylation of programmed death-ligand 1 (PD-L1) in tumor cells as a mechanism of immune evasion during cytotoxic T cell-mediated antitumor responses, and blocking the PD-1/PD-L1 signaling pathway is able to rejuvenate the function of CD8+ T cells recruited by the -SG diet, indicating the potential of combining the -SG diet with immunotherapy. We conducted a single-arm, phase I study (ChiCTR2300067929). The primary outcome suggests that the -SG diet is feasible and safe for regulating systemic immunity. Secondary outcomes include patient tolerability and potential antitumor effects. Collectively, our findings highlight the promising therapeutic potential of the -SG diet for treating solid tumors.

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Publication Details

Journal
Cell Metabolism
Published
2024-11-21
DOI
https://doi.org/10.1016/j.cmet.2024.10.019
Citations
107
Primary Topic
Cancer, Stress, Anesthesia, and Immune Response
Type
article
Field-Weighted Citation Impact
40.87
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article

Dual impacts of serine/glycine-free diet in enhancing antitumor immunity and promoting evasion via PD-L1 lactylation

Nan Lin, Xiaoyue Li, Changtong He, Xiao Liang et al.
107 citations
Cell Metabolism
Cancer, Stress, Anesthesia, and Immune Response
40.87
article

Dual impacts of serine/glycine-free diet in enhancing antitumor immunity and promoting evasion via PD-L1 lactylation

Nan Lin, Xiaoyue Li, Changtong He, Xiao Liang, Xuelei Ma, Zhiwen Long, Yuhao Wei, Yun Hong, Xiang Yu, Jiayi Xu, Hubing Shi, Huan Tong, Liqiang Feng, Aiping Zheng, Jun Yin, Tao Zhang, Yu Zhang, Xinggang Yang, Juan Huang, Linlin Song, Qiang Luo, Xiaomeng Yin, Zhen Lei, Yuting Jiang, Yueyi Li, Guangqi Li, Yunuo Zhao, Renwei Li, Yi Wan, Qianlong Kang, Xiaofan Jing, Z. X. Jiang, Keqin Tan
article en
107 citations

Abstract

The effect of the serine/glycine-free diet (-SG diet) on colorectal cancer (CRC) remains unclear; meanwhile, programmed death-1 (PD-1) inhibitors are less effective for most CRC patients. Here, we demonstrate that the -SG diet inhibits CRC growth and promotes the accumulation of cytotoxic T cells to enhance antitumor immunity. Additionally, we also identified the lactylation of programmed death-ligand 1 (PD-L1) in tumor cells as a mechanism of immune evasion during cytotoxic T cell-mediated antitumor responses, and blocking the PD-1/PD-L1 signaling pathway is able to rejuvenate the function of CD8+ T cells recruited by the -SG diet, indicating the potential of combining the -SG diet with immunotherapy. We conducted a single-arm, phase I study (ChiCTR2300067929). The primary outcome suggests that the -SG diet is feasible and safe for regulating systemic immunity. Secondary outcomes include patient tolerability and potential antitumor effects. Collectively, our findings highlight the promising therapeutic potential of the -SG diet for treating solid tumors.

Cell MetabolismVol. 36(12)
University of Electronic Science and Technology of China (CN), Sichuan University (CN), West China Hospital of Sichuan University (CN), The Recovery Center (US), Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (CN), Sichuan Cancer Hospital (CN), Sichuan Provincial Hospital of Traditional Chinese Medicine (CN)
Zero hunger
Openalex Percentile: Top 0%
Cancer, Stress, Anesthesia, and Immune Response
40.87
DOIOpen Access PDFOpenAlex
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