MCT4, or monocarboxylate transporter 4, is a plasmalemmal transporter that is instrumental in the release of lactate produced by astrocytes through aerobic glycolysis. It is characterized by its lower affinity for lactate compared to other monocarboxylate transporters, with a Km value of approximately 34 mM. MCT4 works in conjunction with MCT1 to facilitate the lactate shuttle, a process critical for the maintenance of lactate homeostasis in various tissues. MCT4 is particularly notable for its high expression in tumors and its role in maintaining intracellular pH homeostasis. Inhibiting MCT4 can suppress tumor growth by enhancing CD8+ T cell infiltration and cytotoxicity, which is linked to the alleviation of acidification in the tumor microenvironment and an increase in chemokine secretion induced by the reactive oxygen species/NF-κB signaling pathway. This suggests that MCT4 has a tumor-intrinsic function in creating an immunosuppressive environment in hepatocellular carcinoma (HCC), and targeting MCT4 could be a promising strategy to enhance the effectiveness of immunotherapy in HCC.
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