Abstract
Lactate blunts the anticancer immune response in breast cancer (BC). However, little is known about the exact effect of lactate transporters such as monocarboxylate transporter 4 (MCT4) on immunotherapy. In this study, we investigated the expression status and prognostic value of MCT4 in BC through large-scale transcriptome data. Our results showed that MCT4 was overexpressed in BC, particularly in the basal-like molecular subtype. Overexpression of MCT4 was significantly correlated with high BC lesion grade and poor prognosis. Enrichment analysis indicated that the MCT4-related genes were involved in immune- and metabolism-related bioprocesses, such as myeloid leukocyte activation, the adaptive immune system, and catabolic process. We also found that the expression of MCT4 in BC lesions was associated with immune cell infiltration and glycolytic rate-limiting enzymes like pyruvate kinase M2 (PKM2) and hexokinases-3 (HK3). Our observations indicate that MCT4 may play a pivotal role in the maintenance of the tumor immune microenvironment (TIME) through metabolic reprogramming. The enzymes of the glycolysis pathway (MCT4, PKM2, and HK3) may thus serve as new targets to modulate the TIME and enhance immunotherapy efficiency.[Figure: see text].