CD28 costimulation drives tumor-infiltrating T cell glycolysis to promote inflammation

• DOI: 10.1172/jci.insight.138729
• Publication Date: 2020-08-19T15:01:22Z
• Authors: Kathryn E. Becker...; Rachel Hongo; Xiang Ye; Kirsten Young; Katie Carbonell; Diana C. Contrera...; Peter J. Siska; Sierra Barone; Caroline E. Roe; Christof C. Smith; Benjamin G. Vincent; Frank M. Mason; Jonathan M. Irish; W. Kimryn Rathmell; Jeffrey C. Rathmell
• Keywords: Anaerobic glycolysis

Metabolic reprogramming dictates the fate and function of stimulated T cells, yet these pathways can be suppressed in cells tumor microenvironments. We previously showed that glycolytic mitochondrial adaptations directly contribute to reducing effector renal cell carcinoma (RCC) CD8+ tumor-infiltrating lymphocytes (TILs). Here we define role metabolic activation functions RCC TILs. CD28 costimulation plays a key augmenting metabolism, is antagonized by inhibitory checkpoint immunotherapy receptors CTLA4 PD-1. While TILs were activated at low level when through receptor alone, addition greatly enhanced activation, function, proliferation. reprogrammed TIL metabolism with increased glycolysis oxidative possibly upregulation GLUT3. Mitochondria also fused greater degree, higher membrane potential overall mass. These phenotypes dependent on glucose as inhibitor 2-deoxyglucose both prevented changes mitochondria function. data show restore rescue supports mass activity.