Abstract
Abstract Emerging data from metabolites-relating trails in cancers demonstrate that a common mechanism of resistance to many novel classes of immune therapeutics is the emergence of immune escape due to the reprogramming of cellular metabolism. Among them, current work about end-metabolites mostly focuses on the intersection between lactate acid, adenosine, reactive oxygen species (ROS), and tumour immune escape. In this article, we aim to review the evidence to date for the dynamic interplay between the three end-metabolites and tumour immune escape for potential approaches to overcome obstacles in the efficacy and durability of immune cancer therapies. We have organized known end-metabolites-associated immune escape mechanisms into three hallmarks: (1) decreased immunogenicity of cancer cells which constitutes defective antigen presentation and the attenuated expression of costimulatory molecules on tumour cells, (2) immunosuppressive microenvironment with aberrant angiogenesis inhibits the differentiation, maturation, and immune deviation of immune cells while drives the activation of immunosuppressive cells by immune-suppressive mediators (cytokines and other factors), (3) immune tolerance retained by inhibitory molecules and depletion of immune cells.
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