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 heterogeneity at diagnosis influences treatment response and survival in multiple myeloma.
Immune heterogeneity at diagnosis influences treatment response and survival in multiple myeloma.
采用最佳截断值(0.394),患者被分为高风险组(n = 231)和低风险组(n = 472)。
现有分期系统尚不能充分反映多发性骨髓瘤(MM)的临床异质性。为确定基线免疫特征能否改进预后判断,研究者对703例新诊断MM患者进行了大规模分析。治疗前采用流式细胞术和多重免疫分析定量外周血免疫细胞亚群及血清细胞因子,并通过时间依赖性ROC分析确定各参数的最佳预后阈值。单变量分析显示,总生存期(OS)较差与CD19 B细胞计数低、CD4/CD8比值低、NK细胞比例高、IL-1、可溶性IL-2受体(sIL-2R)、IL-6、IL-8、IL-10及TNF水平升高,以及补体C3水平低相关。多变量Cox模型将最稳健的预测因素整合为免疫风险评分(IM):IM=0.107×(CD4/CD8)+0.001×sIL-2R+0.003×IL-6+0.006×IL-8−1.238×C3。按最佳截断值0.394将患者分为高危组(n=231)和低危组(n=472)。低危组中位OS显著更长(64.5个月比32.2个月;P<0.0001);在校正临床变量后,IM评分仍为独立预后因素。亚组分析证实该评分在不同治疗背景下均具有预测价值。结果表明,治疗前全身免疫状态是强有力的预后决定因素,并提供了一种可用于临床、基于免疫特征的MM风险分层评分。
The clinical heterogeneity of multiple myeloma (MM) remains incompletely captured by existing staging systems. To determine whether baseline immune profiles could refine prognostication, we conducted a large-scale analysis of 703 newly diagnosed MM patients. Peripheral blood immune subsets and serum cytokines were quantified before treatment via flow cytometry and multiplex immunoassays. Time-dependent ROC analysis identified optimal prognostic thresholds for each parameter. Univariate analysis associated inferior overall survival (OS) with low CD19 B-cell counts, a low CD4 /CD8 ratio, high NK cell percentage, elevated levels of IL-1 , sIL-2R, IL-6, IL-8, IL-10, and TNF, and low complement C3. A multivariate Cox model integrated the most robust predictors into an immune risk score (IM): IM = 0.107 (CD4 /CD8 ) + 0.001 sIL-2R + 0.003 IL-6 + 0.006 IL-8 1.238 C3. Using the optimal cut-off (0.394), patients were stratified into high-risk (n = 231) and low-risk (n = 472) groups. The low-risk group exhibited significantly longer median OS (64.5 months vs. 32.2 months; p < 0.0001), and the IM score remained an independent prognostic factor after adjusting for clinical variables. Subgroup analysis confirmed its predictive value across treatment backgrounds. These results establish the pre-treatment systemic immune state as a powerful prognostic determinant and provide a clinically applicable immune-based scoring system for improved risk stratification in MM.
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