CD147‑mediated reprogrammed glycolytic metabolism potentially induces immune escape in the tumor microenvironment (Review).

Abstract

Impaired antitumor immunity or induced immunosuppression in the tumor microenvironment contributes significantly to tumor progression and resistance to immunotherapy. It is becoming increasingly recognized that dynamic metabolic programming orchestrates appropriate immune responses, whereas incorrect metabolic reprogramming may underlie aberrant immune remodeling. Furthermore, pathways that control cellular metabolism and immune cell function by transcriptional and post‑transcriptional mechanisms are intimately interlinked, including hypo-xia‑inducible factor 1α, c‑Myc and phosphatidylinositol 3‑kinase/protein kinase B/mammalian target of rapamycin signaling. Immunometabolism is an emerging research field involving investigation of the interaction between immunological and metabolic processes. It is likely that high levels of nutrient competition and metabolic interplay exist between tumor cells and infiltrating immune cells in the local tumor milieu, which consequently leads to a reduction in antitumor immunity or immune cell dysfunction. Recently, a metabolic molecular mechanism responsible for the tumorigenic capacity of cluster of differentiation (CD)147, which exhibits high expression on the surface of various malignant tumor cells and is associated with tumor progression via multiple non‑metabolic molecular mechanisms, was identified. The aim of the present review was to focus on the glycolytic mechanism mediated by the upregulation of CD147 in tumors and tumor‑imposed metabolic restrictions on tumor‑infiltrating immune cells, and the consequent immunological hyporesponsiveness. Cellular metabolism is becoming increasingly acknowledged as a key regulator of T‑cell function, specification and fate, and the manipulation of metabolic programming may elucidate therapeutic options for immunological disorders and tumor immunotherapy.