Fueling T-cell Antitumor Immunity: Amino Acid Metabolism Revisited

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.

Automated summary

T cells play a crucial role in eliminating malignant tumors and their activation and differentiation are tightly controlled at multiple levels. Amino acids are essential for T cell antitumor immunity, but their deprivation or accumulation within the tumor microenvironment can diminish T cell functionality. Modulating amino acid metabolism in T cells may be a potential strategy to enhance the efficacy of immunotherapy.