Nature communications · 2025
IKAROS levels are associated with antigen escape in CD19- and CD22-targeted therapies for B-cell malignancies.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Domizi Pablo, Sarno Jolanda, Jager Astraea, Merchant Milton, Pacheco Kaithlen Zen B, Yamada-Hunter Sean A, Rotiroti Maria Caterina, Liu Yuxuan, Baskar Reema, Reynolds Warren D, Sworder Brian J, Sahaf Bita, Bendall Sean C, Mullighan Charles G, Alizadeh Ash A, Leahy Allison B, Myers Regina M, Yates Bonnie, Wang Hao-Wei, Shah Nirali N, Majzner Robbie G, Mackall Crystal L, Grupp Stephan A, Barrett David M, Sotillo Elena, Davis Kara L
Аннотация
Antigen escape relapse is a major challenge in targeted immunotherapies, including CD19- and CD22-directed chimeric antigen receptor (CAR) T-cell for B-cell acute lymphoblastic leukemia (B-ALL). To identify tumor-intrinsic factors driving antigen loss, we perform single-cell analyses on 61 B-ALL patient samples treated with CAR T cells. Here we show that low levels of IKAROS in pro-B-like B-ALL cells before CAR T treatment correlate with antigen escape. IKAROSlow B-ALL cells undergo epigenetic and transcriptional changes that diminish B-cell identity, making them resemble progenitor cells. This shift leads to reduced CD19 and CD22 surface expression. We demonstrate that CD19 and CD22 expression is IKAROS dose-dependent and reversible. Furthermore, IKAROSlow cells exhibit higher resistance to CD19- and CD22-targeted therapies. These findings establish a role for IKAROS as a regulator of antigens targeted by widely used immunotherapies and in the risk of antigen escape relapse, identifying it as a potential prognostic target.