Article Dans Une Revue Cancer Communications Année : 2024

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.
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hal-04791101 , version 1 (19-11-2024)

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Maude Marchais, Marianne Mangeney. FOXO1 or not FOXO1: that is the question. Cancer Communications, 2024, ⟨10.1002/cac2.12624⟩. ⟨hal-04791101⟩
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