Dual Impacts of Serine/Glycine Free Diet in Enhancing Antitumor Immunity and Promoting Evasion via PD-L1 Lactylation [scRNA-Seq]

The effect of Serine/glycine free diet (-SG diet) on colorectal cancer (CRC) remains unclear, meanwhile PD-1 inhibitors are less effective for most CRC patients with proficient mismatch repair/microsatellite stable (pMMR/MSS) characteristics. Here, we demonstrate that -SG diet inhibits CRC growth and promotes the accumulation of cytotoxic T cells to enhance anti-tumor immunity. Additionally, we also identified the lactylation of PD-L1 in tumor cells as a mechanism of immune evasion during cytotocix-T-cell-mediated anti-tumor responses, and blocking PD-1/PD-L1 signaling pathway is able to rejuvenate the function of CD8+ T cells recruited by -SG diet, indicating the clinical potential of combining -SG diet with immunotherapy. Finally, we conducted a single-arm, phase I study, which suggested -SG diet could be a feasible and safe strategy to regulate systemic immunology. Collectively, our findings highlight the promising therapeutic future of -SG diet for treating solid tumors. We collected subcutaneous tumors from mice treated with control diet and -SG diet respectively.