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Yiqiao Qiu, Lin Wang
Cancer Immuno Perspectives ›› 2025, Vol. 1 ›› Issue (1) : 20-30.
PDF(528 KB)
PDF(528 KB)
The metabolic rivalry in tumor microenvironment (TME) is a unifying site of immune abnormality and treatment resistance in tumor. To support unregulated proliferation, tumor cells reorganise their metabolism, including the use of essential nutrients like glucose, amino acids, and lipids and production of toxic metabolic by-products which damage immune effector functions. This has rendered cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, and dendritic cells to be without the necessary substrates to activate and survive, which results in an immunosuppressive niche. This imbalance is further worsened by hypoxia and acidosis which stabilize hypoxia-inducible factors (HIFs) and induces the expression of immune checkpoint molecules including PD-L1. This means that along with inhibiting antitumor immunity, metabolic restrictions prevent the efficacy of immunotherapies, targeted therapies, and chemotherapeutic agents. This is a systematic review that is dedicated to the evaluation of existing information on the role of metabolic competition as the mechanism underlying immune escape and therapy failure, especially glycolysis, amino acid metabolism, and lipid reprogramming. It also analyses emerging treatments of metabolic immunodeficiency, such as IDO-inhibitors, arginase-inhibitors, and lactate-targeted therapy, as a way of restoring immune capacity and improving treatment response. The metabolic interaction between tumor and immunity has been identified as a promising field of research to overcome resistance and augment clinical outcome in cancer therapy.
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