Powering antitumor immunity: challenges & promise at the intersection of immunometabolism & cancer immunotherapy

Since their approval, immune checkpoint inhibitors have drastically altered the landscape of cancer care. However, despite this substantial progress, many agents demonstrating considerable preclinical potential have failed to be successfully translated to the clinic. Therefore, an understanding of the processes underlying T cell responses will be crucial for the rational design of the next generation of immune checkpoint inhibitors. In parallel with these advances in tumor immunology, the field of immunometabolism has identified the importance of metabolic reprogramming during the initial steps of T cell activation in modulating clonal expansion, effector activity, and fate determination. Here, we will highlight the interplay between these processes, their suppression in the tumor-bearing state, and the putative mechanisms by which checkpoint blockade may restore metabolic reprogramming. Finally, we will discuss novel checkpoints under investigation and discovery-driven approaches to identify modulators of immune cell metabolism to synergize with new approaches to immune checkpoint inhibitors .