Alternative activation sensing and signal transduction states define CD7 negative T cell function 3833

Description CD7 negative (CD7-) T cells are a heterogenous and poorly characterized subset making up ∼5% of the human T cell repertoire. Depending on setting, this population has contradictorily been correlated with compromised immune function or potent effector function. CD7- T cells have renewed relevance due to their emerging use in targeting CD7+ T-ALL in CAR T cell therapy. We have previously demonstrated that CD7- T cells have robust antitumor activity when expressing CARs and that this subpopulation is increased in patients responding to CAR T cell therapy. Here, we sought to define the biology that underlies persistence and efficacy of effector CD7- T cells. Our findings demonstrate altered TCR, CD28, and LCK regulation in CD7- T cells upon stimulation. We further observed differences in the activation induced accumulation of receptors that govern T cell proliferation, survival, and metabolism. This includes reduced cell surface expression of receptors known to promote T cell exhaustion through metabolic regulation. Additionally, we performed CD7 KO experiments to uncover whether CD7 is a mechanistic driver of this alternative activation response. CD7 KO failed to recapitulate many of the phenotypic and functional aspects of CD7- T cell biology, suggesting that an imprinted cell state is at play. Our work furthers the functional and molecular understanding of CD7- T cells with immediate implications for their use in immunotherapy.