Tumor-infiltrating T cells are invigorated by modulating cholesterol metabolism

CD8⁺ cytotoxic T cells are fundamental immune cells required for tumor suppression. Under infectious conditions, these cells respond to their corresponding antigen, differentiating to cytotoxic effector T cells. Upon resolution of infection, most effector T cells will undergo contraction while a subset remain, forming immunological memory to protect from subsequent infection. During chronic infection, such as infection with chronic lymphocytic choriomeningitis virus (LCMV), HIV or hepatitis, responding CD8⁺ T cells will undergo what has been termed ‘exhaustion’, in which these cells rapidly lose effector function (1). Importantly, in the context of the tumor microenvironment, where tumor self-antigen can be considered ‘chronic’, CD8⁺ T cells also become exhausted, losing effector function and expressing inhibitory receptors such as PD-1 and CTLA-4 (1,2). Reversing exhaustion of tumor infiltrating effector T cells is considered fundamental for tumor eradication and a key focus of cancer immunotherapy (3).