| Autor: |
Tong, Huan, Jiang, Zedong, Song, Linlin, Tan, Keqin, Yin, Xiaomeng, He, Chengyuan, Huang, Juan, Li, Xiaoyue, Jing, Xiaofan, Yun, Hong, Li, Guangqi, Zhao, Yunuo, Kang, Qianlong, Wei, Yuhao, Li, Renwei, Long, Zhiwen, Yin, Jun, Luo, Qiang, Liang, Xiao, Wan, Yanzhi |
| Zdroj: |
Cell Metabolism; Dec2024, Vol. 36 Issue 12, p2493-25251, 22759p |
| Abstrakt: |
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. [Display omitted] • Serine/glycine-free diet inhibits tumor growth and enhances antitumor immunity • PD-L1 lactylation delays the degradation of PD-L1 in tumor cells by lysosome • PD-L1 lactylation provides a potential target for immunotherapy • Serine/glycine-free diet is proven feasible and safe in clinical trial The serine/glycine-free diet inhibits CRC growth and enhances antitumor immunity but also promotes immune evasion through PD-L1 lactylation. It shows promise when combined with immunotherapy and has been proven feasible and safe in a single-arm, phase I trial. [ABSTRACT FROM AUTHOR] |
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