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Tumor Immunology Adoptive cell therapies using chimeric antigen receptor (CAR) T cells display potent antitumor immunity, but T cell exhaustion can compromise their efficacy. Building on a previous observation that… Click to show full abstract
Tumor Immunology Adoptive cell therapies using chimeric antigen receptor (CAR) T cells display potent antitumor immunity, but T cell exhaustion can compromise their efficacy. Building on a previous observation that interleukin-7 treatment induced polyfunctional CD4+ T cells producing multiple cytokines, Ding et al. expressed a constitutively active variant of the signaling protein STAT5 called CASTAT5 in mouse CD4+ T cells specific for a tumor antigen. CASTAT5-expressing T cells underwent epigenetic remodeling, developed polyfunctionality, and promoted CD8+ T cell–dependent elimination of tumors. In a mouse model of CAR T cells targeting the B cell antigen CD19, CASTAT5 expression in both CD4+ and CD8+ T cells resulted in improved tumor elimination. These findings introduce a new T cell–engineering approach for CAR T cells that could yield improved resistance to exhaustion and more robust antitumor activity. Sci. Immunol. 5 , eaba5962 (2020).