PD-L1 drives metabolic reprogramming and mitochondrial remodeling in NSCLC cells

Metabolic dysregulation in tumor cells often result in the accumulation of byproducts that suppress immune cell function. However, the role of PD-L1 in modulating tumor metabolic remains incompletely understood.

Here, we report that PD-L1 expression in non-small cell lung cancer (NSCLC) cells is associated with increased endocytic activity and alters metabolic flux, particularly within the mitochondrial tricarboxylic acid (TCA) cycle. PD-L1 expression correlates with enhanced mitochondrial fusion and reduced fission, accompanied by changes in the expression of mitochondrial respiratory chain components. Integrated multi-omics analyses further reveal that PD-L1 is linked to alterations in histone methylation, including modifications at the PTPRN2 locus.