Elevated CD10− neutrophils correlate with non-response and poor prognosis of CD19 CAR T-cell therapy for B-cell acute lymphoblastic leukemia

作者：Jinli Zhu, Ji Zhou, Xue Liang, Furun An, Yangyang Ding, Xunyi Jiao, Meng Xiao, Fan Wu, Yingwei Li, Hao Xiao, Ying Pan, Huiping Wang, Zhimin Zhai · 发表于：BMC Medicine · 年份：2025 · DOI：10.1186/s12916-025-03968-5 · 被引用次数：6 · 研究领域：CAR-T cell therapy research、Virus-based gene therapy research、Immunotherapy and Immune Responses

The primary challenges in CD19-specific chimeric antigen receptor T-cell (CD19 CAR T) therapy for patients with refractory/relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL) are non-response and relapse; it is urgent to reveal these mechanisms. Neutrophils play a critical role in the immunosuppressive tumor microenvironment (TME), which can hinder CAR T efficacy. Our previous research identified a subset of immunosuppressive neutrophils with a special phenotype (CD14 − CD10 − CD45 − HLA-DR − SSC ++ , termed CD10 − neuts), which suppress T cell function. Therefore, we speculate that CD10 − neuts may also influence CAR T efficacy, and this study aims to clinically validate this hypothesis. We enrolled 44 patients with r/r B-ALL undergoing CD19 CAR T therapy and 47 healthy controls (HCs). Peripheral blood samples were obtained prior to CAR T infusion to detect CD10 − neuts levels by flow cytometry. Key parameters included the percentage of CD10 − neuts in neutrophils (CD10 − neuts/neutrophils), in all nucleated cells (CD10 − neuts/nucleated cells), and the absolute count of CD10 − neuts. We analyzed the correlations between these indicators and therapeutic response, relapse-free survival (RFS), overall survival (OS), and CAR T cell persistence time. CD10 − neuts levels were significantly elevated in patients with r/r B-ALL compared to HCs. Additionally, non-responding patients exhibited higher CD10 − neuts levels than those in remission. Specifically, CD10 − neuts/neutroph...