MCT4在肿瘤代谢与免疫调控中的双重作用机制研究

In hypoxic environments, tumor cells can maintain metabolic homeostasis through lactate shuttling mediated by monocarboxylate transporters (MCTs), with MCT1, MCT2, and MCT4 being the core subtypes involved in lactate transport. Notably, MCT4 is highly expressed on the surface of tumor cells, where it not only pumps lactate out into the tumor microenvironment (TME) to support tumor proliferation and invasion but also participates in lactate metabolism regulation in ischemic diseases. Due to its role as a "key metabolic hub" in tumors and other pathological processes, MCT4 has become a focus of research in the field. In the context of anti-tumor therapy, inhibiting MCT4 function (e.g., using small molecule inhibitors such as AZD3965 and α-cyano-4-hydroxycinnamic acid (CHC)) can effectively block lactate efflux from tumor cells, leading to intracellular acidosis and energy depletion, ultimately suppressing tumor growth. This study further elucidates non-canonical regulatory roles of MCT4: MCT4 not only participates in tumor progression through lactate metabolism but also directly interacts with PD-L1, thereby modulating H3K18la and PD-L1 glycosylation levels. Additionally, the study confirms that the Wnt/β-catenin pathway can act as an upstream signal to regulate histone lactylation. Treatment with the Wnt pathway inhibitor XAV939 significantly downregulates both H3K18la and PD-L1 glycosylation levels, further refining the association mechanism between "metabolism-epigenetics-immune regulation."