Cancer and Immune Cells: A Metabolic Battle in the Tumor Microenvironment Publisher Pubmed



Pournezhad S ; Azar R ; Taghizadehhesary F
Source: Cancer Treatment and Research Published:2026

Abstract

Immunometabolism has emerged as a critical field that links cellular energy regulation with immune function, including in the context of cancer. The tumor microenvironment (TME) is characterized by hypoxia, acidosis, and nutrient competition, all of which promote metabolic reprogramming in cancer cells while suppressing immune surveillance. Antitumor immune cells such as cytotoxic T lymphocytes, natural killer (NK) cells, and M1 macrophages rely on glycolysis and oxidative phosphorylation to sustain effector functions. In contrast, tumor-promoting cells, including regulatory T cells, myeloid-derived suppressor cells, and M2 macrophages, adopt oxidative metabolism and immunosuppressive pathways that reinforce immune escape. Cancer cells further evade immunity through immune checkpoint expression, reduced antigen presentation, secretion of suppressive cytokines, and mitochondrial hijacking, gaining bioenergetic superiority over immune cells. Current immunotherapies, such as checkpoint inhibitors, CAR-T cell therapy, cancer vaccines, and NK-cell–based therapies, have transformed cancer treatment but are often limited by TME-induced metabolic suppression. This chapter highlights the central role of metabolism in cancer–immune dynamics and introduces a novel therapeutic framework that integrates metabolic intervention with immune activation for improved cancer treatment outcomes. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2026.