Cancer immunometabolism: advent, challenges, and perspective

For decades, great strides have been made in the field of immunometabolism. A plethora of evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism to the center stage of innate and adaptive immunomodulation. Given this, we focus on changes in immunometabolism, a converging series of biochemical events that alters immune cell function, propose the immune roles played by diversified metabolic derivatives and enzymes, emphasize the key metabolism-related checkpoints in distinct immune cell types, and discuss the ongoing and upcoming realities of clinical treatment. It is expected that future research will reduce the current limitations of immunotherapy and provide a positive hand in immune responses to exert a broader therapeutic role. 1. Attempting to delineate the complex and multidimensional interplays between metabolites (or metabolic enzymes) and predominant immune cell populations.2. Metabolic checkpoints of immune cells are described and the contribution of these metabolic targets to determine the metabolic adaptations of distinct immune cells in specific tissue environments is emphasized.3. Proposed cancer-immunometabolism subcycle, enriching the theoretical foundation of the cancer-immunology field.4. Metabolism-induced disturbances in the acid-base balance of the tumor microenvironment have non-redundant effects on immunotherapy.5. Pending challenges and clinical concerns in metabolic insights were addressed.