Research ArticleTUMOR IMMUNOLOGY

Persistent STAT5 activation reprograms the epigenetic landscape in CD4+ T cells to drive polyfunctionality and antitumor immunity

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Science Immunology  30 Oct 2020:
Vol. 5, Issue 52, eaba5962
DOI: 10.1126/sciimmunol.aba5962

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CAR T cells get a STAT tune-up

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 STAT5 variant (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.

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