The Role of Lactate in Cancer Immunotherapy: Mechanisms and Applications.

Abstract

In recent years, immunotherapy has demonstrated significant clinical effectiveness. However, challenges such as low response rates, severe treatment-related side effects, and acquired immune tolerance persist in tumor immunotherapy. Metabolic dysregulation is acknowledged as a principal factor in tumor growth, with aerobic glycolysis, or the Warburg effect, being a defining characteristic of numerous cancers. The enhanced uptake of glucose and glycolysis provides the necessary intermediates for anabolic reactions, which are essential for the proliferation of cancer cells, while simultaneously supplying sufficient energy. How-ever, the concomitant increase in lactate production contributes to immunosuppression within the tumor microenvironment. Tumor cells exploit lactate anabolism, lactate shuttling, and ly-sine lactylation modifications, which significantly diminish the efficacy of immunotherapy. The treatment targeting lactate anabolism or lactate transport proteins may prove an effective strategy for enhancing the effectiveness of cancer immunotherapy. This review provides a comprehensive overview of the role of lactate in anti-tumor immunotherapy, with the objective of deepening the understanding of the importance of lactate monitoring in cancer treatment. By elucidating these mechanisms, we aim to suggest innovative avenues for clinical cancer management, potentially improving therapeutic outcomes and overcoming the existing limita-tions of immunotherapy.