CAR T cells for solid tumors: genome-wide dysfunction signature confirms value of c-Jun overexpression, but signals heterogeneity

Abstract

Chimeric antigen receptor (CAR) T cells still have limited effects in cancer, and especially in solid tumors, due to T cell dysfunction and exhaustion. CAR T cells overexpressing c-Jun (JUN CAR T cells) have been introduced to solve this problem. In this paper, we analyze JUN CAR T cells scRNA-seq data in solid tumors, by applying a genome-wide signature of T cell dysfunction, TID. This signature comes from the bulk RNA-seq signature TIDE, introduced to predict immune checkpoint inhibitor response. Our analysis confirms that on average, JUN CAR T cells are less dysfunctional than non-JUN CAR T cells. However, it also shows heterogeneity within JUN CAR T cells, which brings uncertainty about possible tumor resistance. We conclude that genome-wide dysfunction signature TID helps de-risking CAR T cell therapy for solid tumors.