Nanotechnology Reprogramming Metabolism for Enhanced Tumor Immunotherapy.

Abstract

Mutation burden, hypoxia, and immunoediting contribute to altered metabolic profiles in tumor cells, resulting in a tumor microenvironment (TME) characterized by accumulation of toxic metabolites and depletion of various nutrients, which significantly hinder the antitumor immunity <i>via</i> multiple mechanisms, hindering the efficacy of tumor immunotherapies. In-depth investigation of the mechanisms underlying these phenomena are vital for developing effective antitumor drugs and therapies, while the therapeutic effects of metabolism-targeting drugs are restricted by off-target toxicity toward effector immune cells and high dosage-mediated side effects. Nanotechnologies, which exhibit versatility and plasticity in targeted delivery and metabolism modulation, have been widely applied to boost tumor immunometabolic therapies <i>via</i> multiple strategies, including targeting of metabolic pathways. In this review, recent advances in understanding the roles of tumor cell metabolism in both immunoevasion and immunosuppression are reviewed, and nanotechnology-based metabolic reprogramming strategies for enhanced tumor immunotherapies are discussed.