Targeting lactate metabolism in the tumor microenvironment: Immunomodulation and prospects for antitumor therapy

Disturbed lactate metabolism in the tumor microenvironment (TME) is a key factor driving malignant tumor progression. Recent studies have revealed that lactate is not only a metabolic by-product of glycolysis, but also an important signaling molecule that regulates tumor cell and immune cell functions. Lactate remodels TME through metabolic-signaling-immune interactions, inhibits the activity of effector immune cells, and promotes the expansion of immunosuppressive cells, thus weakening the anti-tumor immune response. This review systematically describes the regulatory network of lactate metabolism in the TME, focuses on analyzing the role of lactate on different immune cells, and explores innovative therapeutic strategies and clinical translational pathways that target lactate production/transport, neutralize the acidic environment, and multi-target remodeling of lactate homeostasis by traditional Chinese medicine (TCM), which will provide the basis for the formulation of precise antitumor treatment protocols based on metabolic remodeling and optimization of novel combinatorial therapies, and ultimately achieve an overall enhancement of the effectiveness of clinical cancer treatment.