Fig. 2
From: Exhaustion of CAR T cells: potential causes and solutions
Signal transduction underlying chimeric antigen receptor (CAR)-induced exhaustion. Tonic signaling from aggregated 28z CAR induce the expression of exhaustion-related genes by modifying the epigenome. Inhibition of signals from inhibitory receptors does not revert the epigenomic status and recovers exhausted CAR T cells only transiently. The exhaustion-related epigenome can be reversed by the cessation of tonic signal emanating from CAR. BBz CAR generates TRAF-mediated non-canonical NF-κB (ncNF-κB) signal and induce memory T cell related gene expression