Coaching tumor-infiltrating CD8+ T cells to eat right

At least in experimental animals the efficacy of active immunotherapy of cancer can be increased by metabolic reprogramming of tumor antigen (TA)-specific CD8+ T cells towards fatty acid (FA) catabolism and away from glycolysis [1]. In a nutshell, TA-specific CD8+ T cells or T cells with a chimeric antigen receptor (CAR) directed to a surface-expressed TA are hampered in their efforts to combat cancers by rapid loss of functions once they enter the tumor microenvironment (TME). This exhaustion, accompanied by increased cell surface expression of check point inhibitors was originally attributed to chronic TA-driven stimulation of CD8+ tumor infiltrating lymphocytes (TILs) [2]. Exhaustion of bystander CD8+ TILs, directed to antigens not present within the TME, contradicts this notion but rather points towards a different mechanism