Fueling T-cell Antitumor Immunity: Amino Acid Metabolism Revisited
Cet article analyse le lien entre le métabolisme des acides aminés et le devenir des lymphocytes T, résume les mécanismes par lesquels la privation d'acides aminés ou l'accumulation de certains métabolites d'acides aminés dans le microenvironnement tumoral réduit la fonction des lymphocytes T, puis examine l'intérêt de stratégies thérapeutiques potentielles consistant à cibler le métabolisme des acides aminés à l'intérieur des lymphocytes T ou en dehors
T cells are the key players in eliminating malignant tumors. Adoptive transfer of tumor antigen-specific T cells and immune checkpoint blockade has yielded durable antitumor responses in the clinic, but not all patients respond initially and some that do respond eventually have tumor progression. Thus, new approaches to enhance the utility of immunotherapy are needed. T-cell activation and differentiation status are tightly controlled at the transcriptional, epigenetic, and metabolic levels. Amino acids are involved in multiple steps of T-cell antitumor immunity, including T-cell activation, proliferation, effector function, memory formation as well as functional exhaustion. In this review, we briefly discuss how amino acid metabolism is linked to T-cell fate decisions and summarize how amino acid deprivation or accumulation of certain amino acid metabolites within the tumor microenvironment diminishes T-cell functionality. Furthermore, we discuss potential strategies for immunotherapy via modulating amino acid metabolism either in T cells intrinsically or extrinsically to achieve therapeutic efficacy.
Cancer Immunology Research , résumé, 2020