Lactylation stabilizes PD-L1 to promote tumor immune evasion and cell growth - PubMed
5 hours ago
- #tumor immune evasion
- #lactylation
- #PD-L1
- Lactate in the tumor microenvironment upregulates PD-L1 expression via lysine lactylation (Kla) at residue K280.
- Lactylation stabilizes PD-L1 by inhibiting E3 ligase HUWE1 binding, ubiquitination, and proteasomal degradation.
- Alanyl-tRNA synthetase 1 (AARS1) is identified as the lactyltransferase responsible for PD-L1 K280 lactylation.
- PD-L1 lactylation promotes tumor immune evasion by impairing CD8+ T cell-mediated cytotoxicity and accelerates tumor growth.
- Sodium lactate (NaLa) administration enhances the efficacy of anti-PD-L1 immunotherapy in preclinical models.
- PD-L1 K280 lactylation correlates with advanced non-small cell lung cancer stages and poor patient survival.
- The findings propose lactylation as a therapeutic target to augment immune checkpoint blockade efficacy.