Unveiling cell metabolic bioprocess of programmed cell death ligand 1 (PD-L1) expression through nutrients-driven cancer immunomarker progression using SERS technique

Abstract

Abstract In recent years, the expression and progression of programmed cell death ligand 1 (PD-L1) as an immunomarker in the context of cell metabolic environments have gained significant attention in cancer research. This study aims to explore the dynamic changes of PD-L1 expression and progression within the cell metabolic environment using SERS. The SERS technique offers a sensitive, rapid, and powerful analytical tool that allows for targeted and non-destructive detection of immunomarker with high-sensitivity and specificity. By combining SERS with cell metabolic state-profiling, we investigated the correlation between the metabolic state of cells and PD-L1 immunomarker expression. We assessed the changes in PD-L1 expression under different metabolic states including glucose deprivation, metabolic co-enzyme activity, and altered metabolic cytokines availability. SERS nanotags based on aptamer combined Au/4-ATP/Ag were employed in cells, providing molecular fingerprints of the Raman reporter in cells that reflected the PD-L1 expression levels. Our intricate exploration utilizing PD-L1-aptamer functionalized SERS nanotags underscores the intricate modulation of PD-L1 expression across diverse cellular scenarios. Specifically, we observed that glucose deprivation led to upregulated PD-L1 expression, suggesting a potential link between cellular energy metabolism and immune checkpoint regulation. Additionally, NADPH lead glucose metabolism was found to significantly influence PD-L1 expression dynamics. Our results elucidate concentration-dependent PD-L1 responses to immune signaling molecules, illuminating the sophisticated interplay between glucose metabolism, redox dynamics, and cytokine-mediated regulation in shaping immune checkpoint expression. These findings hold implications for precision-targeted therapeutic interventions in the realm of cancer treatment.