肿瘤细胞治疗研究
英文原题：A single-cell atlas of multiple myeloma defines malignant archetypes and proliferative states.
这些数据为浆细胞恶性肿瘤的患者分层和精准靶点提名提供了临床可操作的蓝图。
多发性骨髓瘤（MM）是一种浆细胞恶性肿瘤，具有广泛的基因组和转录异质性，限制了疾病分类和精准治疗。在此，我们构建了一个来自341例个体、涵盖疾病及治疗连续过程的临床注释、群体规模的单细胞MM图谱。我们识别出五种复发性恶性转录原型，以及与基因组特征、治疗耐药和临床结局相关的正交增殖程序。在独立的CoMMpass队列中的验证证明了其稳健性、预后相关性以及跨平台的可移植性。我们开发了一个单细胞靶点发现流程，优先考虑恶性富集、细胞类型特异性和组织限制性，鉴定出FCRL2为一个由恶性浆细胞表达的浆细胞限制性或B细胞谱系限制性表面靶点。靶向FCRL2的CAR-T 细胞在体外表现出抗原特异性活性，并在体内显示出生存获益。总之，这些数据为浆细胞恶性肿瘤中的患者分层和精准靶点提名提供了具有临床可操作性的蓝图。
Multiple myeloma (MM) is a plasma-cell malignancy with extensive genomic and transcriptional heterogeneity, limiting disease classification and precision therapy. Here we generated a clinically annotated, population-scale, single-cell atlas of MM from 341 individuals spanning the disease and treatment continuum. We identified five recurrent malignant transcriptional archetypes and an orthogonal proliferative program associated with genomic features, therapeutic resistance and clinical outcomes. Validation in the independent CoMMpass cohort demonstrated robustness, prognostic relevance and portability across platforms. We developed a single-cell, target-discovery pipeline prioritizing malignant enrichment, cell-type specificity and tissue restriction, identifying FCRL2 as a plasma-restricted or B cell-lineage-restricted surface target expressed by malignant plasma cells. FCRL2-targeted chimeric antigen receptor T cells demonstrated antigen-specific activity in vitro and survival benefit in vivo. Together, these data provide a clinically actionable blueprint for patient stratification and precision target nomination in plasma-cell malignancies.
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