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.
Competing Interests: Declaration of interests The authors C.H. and Z. Lei are shareholders and board members of Recovery Plus Clinic Co., which develops medical digital devices and nutritional powder for clinicians. Z. Long and J.Y. are also members of this company. Additionally, Recovery Plus Clinic Co. funded the targeted amino acid metabolism and some other sequencing services for this project. Their involvement could potentially bias the results, but independent analyses and unaffiliated researchers were included for study design and data analysis to minimize this possible risk.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)