Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy

• Published in: Journal of hematology and oncology 2023-06, Vol.16 (1), p.59-59, Article 59
• Main Authors: Yang, Luming, Chu, Zhaole, Liu, Meng, Zou, Qiang, Li, Jinyang, Liu, Qin, Wang, Yazhou, Wang, Tao, Xiang, Junyu, Wang, Bin
• Format: Article
• Language: English
• Subjects: Amino acids; Amino Acids - metabolism; Antigens; Cancer; Cancer immunotherapy; Care and treatment; Cell differentiation; Cytokines; Cytotoxicity; Disease susceptibility; Drug therapy; Energy Metabolism; Enzymes; Health aspects; Hematology; Homeostasis; Humans; Immune cells; Immune response; Immunity; Immunotherapy; Lymphocytes; Metabolism; Metabolites; Metastases; mTOR; Neoplasms - drug therapy; Nutrients; Oncology; Phenotypes; Physiological aspects; Protein synthesis; Proteins; Review; Roles; Sensors; SLC transporters; T cell receptors; TOR protein; Tumor Microenvironment; Tumor-infiltrating lymphocytes; Tumorigenesis; Tumors
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-023-01453-1

Amino acids are basic nutrients for immune cells during organ development, tissue homeostasis, and the immune response. Regarding metabolic reprogramming in the tumor microenvironment, dysregulation of amino acid consumption in immune cells is an important underlying mechanism leading to impaired anti-tumor immunity. Emerging studies have revealed that altered amino acid metabolism is tightly linked to tumor outgrowth, metastasis, and therapeutic resistance through governing the fate of various immune cells. During these processes, the concentration of free amino acids, their membrane bound transporters, key metabolic enzymes, and sensors such as mTOR and GCN2 play critical roles in controlling immune cell differentiation and function. As such, anti-cancer immune responses could be enhanced by supplement of specific essential amino acids, or targeting the metabolic enzymes or their sensors, thereby developing novel adjuvant immune therapeutic modalities. To further dissect metabolic regulation of anti-tumor immunity, this review summarizes the regulatory mechanisms governing reprogramming of amino acid metabolism and their effects on the phenotypes and functions of tumor-infiltrating immune cells to propose novel approaches that could be exploited to rewire amino acid metabolism and enhance cancer immunotherapy.