肿瘤细胞治疗研究
英文原题：CAR-T cells with the CD38(-)CD73(-)Tim-3(-)HLA-DR(+) phenotype predict the efficacy of tisagenlecleucel as a treatment for B cell precursor ALL.
本研究入组 19 例 BCP-ALL 患者（16 例儿童和 3 例年轻成人），接受 tisagenlecleucel 治疗。
抗CD19CAR-T 细胞疗法对B细胞前体急性淋巴细胞白血病（BCP-ALL）疗效显著，但约半数患者会复发，因此迫切需要找到提高疗效的因素。本研究纳入19例接受tisagenlecleucel治疗的BCP-ALL患者，包括16名儿童和3名青年。研究在CAR-T细胞输注前后采集输注产品、外周血和骨髓样本。单细胞分析显示，长期应答者中的中央记忆CAR阳性T细胞增加；而复发患者输注后富集CXCR3⁺ CD38高表达 PD-1高表达效应型CAR阳性T细胞。相比之下，长期应答者的输注产品中富集CD38⁻ CD73⁻ Tim-3⁻ HLA-DR⁺表型CAR阳性T细胞，其特征包括腺苷生成能力降低、转录组呈记忆样特征，以及利用线粒体代谢和氧化磷酸化。本研究揭示，CD38⁻ CD73⁻ Tim-3⁻ HLA-DR⁺表型有助于接受tisagenlecleucel治疗的BCP-ALL患者实现长期缓解。
Anti-CD19 chimeric antigen receptor T cell (CAR-T) therapy is highly effective for B cell precursor acute lymphoblastic leukemia (BCP-ALL); however, approximately half of the patients relapse. Thus, there is an urgent need to identify factors that improve efficacy. This study enrolls 19 patients with BCP-ALL (16 children and 3 young adults) who receive tisagenlecleucel. Infusion products, peripheral blood, and bone marrow samples are obtained before and after CAR-T cell infusion. Single-cell analysis reveals that central memory CAR pos T cells increase in long-term responders, whereas CXCR3 + CD38 high PD-1 high effector CAR pos T cells are enriched in relapsed patients, post-infusion. By contrast, CAR pos T cells obtained from infusion products in long-term responders are enriched in the CD38 - CD73 - Tim-3 - HLA-DR + phenotype, characterized by a decreased ability to produce adenosine, memory-like transcriptomic characteristics, and leveraging of mitochondrial metabolism and oxidative phosphorylation. Our study reveals that the CD38 - CD73 - Tim-3 - HLA-DR + phenotype contributes to long-term remission in patients with BCP-ALL who receive tisagenlecleucel.
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