PD-L1 is associated with metabolic adaptation and mitochondrial remodeling in NSCLC cells

Abstract Tumor metabolism is governed by a complex network of processes that can influence immune evasion. Metabolic dysregulation in tumor cells can lead to the accumulation of metabolites that may influence immune cell function. However, the relationship between PD-L1 expression and tumor cell metabolism 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 altered metabolic flux, particularly in the tricarboxylic acid (TCA) cycle. PD-L1 expression is aleo associated with mitochondrial remodeling, including alterations in proteins involved in mitochondrial fusion and fission and in mitochondrial respiratory chain components. Integrated multi-omics analyses further identified differential H3K9me3 patterns associated with differences in PD-L1 expression status, including differential H3K9me3 patterns at the PTPRN2 locus. Collectively, our findings suggest that differences in PD-L1 expression status are associated with metabolic, mitochondrial, and epigenetic alterations in NSCLC cells.