Influence of lactate in resistance to anti‑PD‑1/PD‑L1 therapy: Mechanisms and clinical applications (Review)

Abstract

Metabolic reprogramming is a prominent characteristic of tumor cells, evidenced by heightened secretion of lactate, which is linked to tumor progression. Furthermore, the accumulation of lactate in the tumor microenvironment (TME) influences immune cell activity, including the activity of macrophages, dendritic cells and T cells, fostering an immunosuppressive milieu. Anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy is associated with a prolonged survival time of patients with non-small cell lung cancer. However, some patients still develop resistance to anti-PD-1/PD-L1 therapy. Lactate is associated with resistance to anti-PD-1/PD-L1 therapy. The present review summarizes what is known about lactate metabolism in tumor cells and how it affects immune cell function. In addition, the present review emphasizes the relationship between lactate secretion and immunotherapy resistance. The present review also explores the potential for targeting lactate within the TME to enhance the efficacy of immunotherapy.