决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Immune biomarkers of increased infection risk in multiple myeloma.
为了弥补这一知识空白并识别感染风险增加的免疫生物标志物,我们对1786名处于不同疾病阶段和治疗方案下的患者的骨髓和外周血样本,采用下一代流式细胞术进行了免疫分析。
感染仍是多发性骨髓瘤发病的主要原因。预防感染至关重要,而免疫分析可反映宿主、肿瘤及治疗相关免疫抑制的累积效应。然而,目前对免疫功能障碍及其与感染关联的认识仍有限。为填补这一知识空白并识别感染风险增加的免疫生物标志物,我们对1786例处于不同疾病阶段和治疗场景患者的骨髓和外周血样本,采用下一代流式细胞术进行了免疫分析。发生感染的患者骨髓中CD27+ B细胞和CD27-NK 细胞百分比显著降低,CD27-/CD27+ T细胞比值升高。这些免疫风险因素在3个独立数据集中得到验证。我们开发了一个免疫评分,将患者按上述风险因素≤1个 vs ≥2个进行分层,其与更高的感染发生率相关(35% vs 60%,P< .001)。免疫评分(比值比,2.31;P< .001)、疾病分期以及CD38-、B细胞成熟抗原-或G蛋白偶联受体C类第5组成员D靶向治疗与感染发生率独立相关。骨髓和外周血中可检测到的所有细胞类型均显著相关,提示感染风险增加的免疫生物标志物可通过常规实验室可及的微创方法进行监测。
Infection remains a leading cause of morbidity in multiple myeloma. Preventing infections is paramount and immune profiling could reflect the cumulative effect of host-, tumor-, and treatment-related immunosuppression. However, current understanding of immune dysfunction and its association with infection is limited. To address this gap in knowledge and identify immune biomarkers of increased infection risk, we performed immune profiling using next-generation flow cytometry in bone marrow and peripheral blood samples from 1786 patients at various disease stages and treatment scenarios. Patients developing infection had significantly lower percentages of CD27+ B cells and CD27- natural killer cells, as well as an increased CD27-/CD27+ T-cell ratio in the bone marrow. These immune risk factors were validated in 3 independent data sets. An immune score was developed to stratify patients with ≤1 vs ≥2 of the aforementioned risk factors, which was associated with higher infection incidence (35% vs 60%, P< .001). The immune score (odds ratio, 2.31; P< .001), disease stage, and CD38-, B-cell maturation antigen-, or G protein-coupled receptor class C group 5 member D-targeted therapy were independently associated with infection incidence. All cell types detectable in the bone marrow and peripheral blood were significantly correlated, suggesting that immune biomarkers of increased infection risk could be monitored using minimally invasive methods that are available in routine laboratories.
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