FOXO1 or not FOXO1: that is the question
Résumé
Two recently published studies have uncovered a critical yet complex role of the transcription factor FOXO1 in enhancing CAR-T cell antitumor efficacy. Surprisingly, while FOXO1 overexpression in activated CAR-T cells boosts their effectiveness, other research reveals that inhibiting FOXO1 in quiescent T cells produces non-activated CAR-T cells with greater tumor-killing capabilities than ex-vivo activated CAR-T cells. Here we propose a model that reconciles these seemingly conflicting data. Experimental data show that both strategies lead T cells to an optimal activation state : overexpressing FOXO1 in activated T cells prevents them from reaching a detrimental late activation state, while inhibiting FOXO1 in quiescent T advances them to a highly effective intermediate activation state. This insight underscores the critical need to finely tune FOXO1 activity and T cell activation to unlock the full potential of CAR-T cell therapies.
Domaines
Sciences du Vivant [q-bio]
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Cancer Communications - 2024 - Marchais - FOXO1 or not FOXO1 that is the question.pdf (538.23 Ko)
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