近日，四川大学马学磊等研究人员合作揭示，无丝氨酸/甘氨酸饮食对于增强抗肿瘤免疫和通过PD-L1乳酸化促进逃避的双重影响。相关论文于2024年11月21日在线发表在《细胞—代谢》杂志上。

研究人员表示，无丝氨酸/甘氨酸饮食（SG饮食）对结直肠癌（CRC）的影响尚不清楚；同时，程序性死亡-1 （PD-1）抑制剂对大多数CRC患者效果较差。

研究人员证明，SG饮食抑制结直肠癌的生长，促进细胞毒性T细胞的积累，进而增强抗肿瘤免疫。此外，研究人员还发现肿瘤细胞中程序性死亡配体1 （PD-L1）的乳酸化是细胞毒性T细胞介导的抗肿瘤反应中免疫逃避的一种机制。阻断PD-1/PD-L1信号通路能够恢复由SG饮食募集的CD8⁺ T细胞的功能，这表明将SG饮食与免疫治疗结合起来的潜力。

研究人员进行了一项单臂I期研究（ChiCTR2300067929）。初步结果表明，SG饮食对调节全身免疫是可行和安全的。次要结局包括患者耐受性和潜在的抗肿瘤作用。总的来说，这些发现强调了SG饮食治疗实体肿瘤的有希望的治疗潜力。

附：英文原文

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

Author: Huan Tong, Zedong Jiang, Linlin Song, Keqin Tan, Xiaomeng Yin, Chengyuan He, Juan Huang, Xiaoyue Li, Xiaofan Jing, Hong Yun, Guangqi Li, Yunuo Zhao, Qianlong Kang, Yuhao Wei, Renwei Li, Zhiwen Long, Jun Yin, Qiang Luo, Xiao Liang, Yanzhi Wan, Aiping Zheng, Nan Lin, Tao Zhang, Jiayi Xu, Xinggang Yang, Yuting Jiang, Yueyi Li, Yu Xiang, Yu Zhang, Lusi Feng, Zhen Lei, Hubing Shi, Xuelei Ma

Issue&Volume: 2024-11-21

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.

DOI: 10.1016/j.cmet.2024.10.019

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00415-7