CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:B-cell activating factor receptor expression in B-lymphoblastic leukaemia: Flow cytometric analysis and implications for targeted therapy.
B-cell activating factor receptor expression in B-lymphoblastic leukaemia: Flow cytometric analysis and implications for targeted therapy.
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分化簇19(CD19)靶向治疗显著改善了B细胞恶性肿瘤的预后;然而,由抗原逃逸驱动的复发仍是主要的临床挑战,凸显了对替代治疗靶点的需求。B细胞活化因子受体(BAFF-R)是B细胞存活的关键调节因子,在成熟B细胞肿瘤中高表达,但其在B淋巴母细胞白血病(B-ALL)中的相关性仍不明确。
我们使用多参数流式细胞术评估了诊断时和复发时新鲜B-ALL样本中的BAFF-R表达。BAFF-R在大多数病例中持续表达,尽管水平低于成熟B细胞,并且在CD19靶向治疗后的大多数CD19阴性复发中表达得以保留。
值得注意的是,肿瘤蛋白p53(TP53)改变在CD19阴性免疫逃逸疾病中显著富集(68.8% vs. 21.7%;p = 0.0006;OR = 7.9),然而BAFF-R表达在该高危组中仍得以保留。这些发现确立了BAFF-R作为B-ALL中稳定的免疫治疗靶点,包括在CD19阴性和TP53改变的复发性疾病中,并强调了其在正在进行的BAFF-R靶向嵌合抗原受体(CAR)T细胞治疗早期临床试验中的相关性。
Cluster of differrentiation 19 (CD19)-directed therapies have significantly improved outcomes in B-cell malignancies; however, relapse driven by antigen escape remains a major clinical challenge, underscoring the need for alternative therapeutic targets. The B-cell activating factor receptor (BAFF-R), a key regulator of B-cell survival, is highly expressed in mature B-cell neoplasms, but its relevance in B-lymphoblastic leukaemia (B-ALL) remains unclear.
We assessed BAFF-R expression in diagnostic and relapsed fresh B-ALL samples using multi-parameter flow cytometry. BAFF-R was consistently expressed in most cases, albeit at lower levels than in mature B cells, and expression was retained in the majority of CD19-negative relapses following CD19-directed therapy.
Notably, tumor protein p53 (TP53) alterations were significantly enriched in CD19-negative immune escape disease (68. 8% vs. 21. 7%; p = 0. 0006; OR = 7. 9), yet BAFF-R expression remained preserved in this high-risk group.
These findings establish BAFF-R as a stable immunotherapeutic target in B-ALL, including in CD19-negative and TP53-altered relapsed disease, and underscore its relevance amid ongoing early-phase clinical trials of BAFF-R-directed chimeric antigen receptor (CAR) T-cell therapy.
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