Identification of vitamin B6 as a PD-L1 suppressor and an adjuvant for cancer immunotherapy.

Abstract

Interaction of programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) inhibits T cell activation. Tumor tissues can evade immune surveillance by expressing higher levels of PD-L1. Identification of potential regulators of PD-L1 through natural metabolites may contribute to discovering new drugs for immunotherapy. By using a metabolite library screen, we showed that pyridoxal (PL) significantly suppresses PD-L1 expression. Mechanistically, PL accelerates PD-L1 degradation in a proteasome-dependent manner, and STUB1 serves as an E3 ligase during the process. Functionally, PL enhances T cell killing activity by blocking the PD-1/PD-L1 signaling pathway. Thus, we have identified PL as an inhibitor of PD-L1, which provides a feasible option for combination immunotherapy.

• Authors: Jinwei Yuan, Jianlong Li, Man Shang, Yuan Fu, Ting Wang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 561 Pg. 187-194 (07 05 2021) ISSN: 1090-2104 [Electronic] United States
• PMID: 34023785 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• B7-H1 Antigen
• CD274 protein, human
• Vitamin B Complex
• Vitamin B 6
• STUB1 protein, human
• Ubiquitin-Protein Ligases

Topics

• B7-H1 Antigen (antagonists & inhibitors, immunology)
• Cells, Cultured
• Humans
• Immunotherapy (methods)
• Neoplasms (drug therapy, immunology, metabolism)
• Proteolysis
• Signal Transduction
• T-Lymphocytes (immunology)
• Ubiquitin-Protein Ligases (metabolism)
• Vitamin B 6 (pharmacology)
• Vitamin B Complex (pharmacology)