Targeting tumor-intrinsic SLC16A3 to enhance anti-PD-1 efficacy via tumor immune microenvironment reprogramming

Immunotherapy, especially immune checkpoint inhibitors, has revolutionized clinical practice within the last decade. However, primary and secondary resistance to immunotherapy is common in patients with diverse types of cancer. It is well-acknowledged that tumor cells can facilitate the formation of immunosuppressive microenvironments via metabolism reprogramming, and lactic acid, the metabolite of glycolysis, is a significant contributor. SLC16A3 (also named as MCT4) is a transporter mediating lactic acid efflux. In this study, we investigated the role of glycolysis in immunotherapy resistance and aimed to improve the immunotherapy effects via Slc16a3 inhibition. Bioinformatical analysis revealed that the expression of glycolysis-related genes correlated with less CD8