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:Peripheral blood immune profiling reveals key signatures in newly diagnosed NK/T cell lymphoma patients.
Peripheral blood immune profiling reveals key signatures in newly diagnosed NK/T cell lymphoma patients.
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我们揭示了新诊断 NK/T 细胞淋巴瘤患者 PBMC 的动态变化,并鉴定了细胞内 EBV 高载量患者的特异性特征。我们的发现为 NKTCL 的免疫发病机制提供了新见解,为基于免疫的分层及治疗策略的开发提供了有价值的信息。
自然杀伤/T细胞淋巴瘤(NKTCL)是一种侵袭性EB病毒(EBV)相关非霍奇金淋巴瘤,预后较差。近期对肿瘤组织的基因组学和转录组学研究增进了我们对NKTCL发病机制的理解,但初诊时的全身免疫特征仍未完全阐明。
本研究通过单细胞RNA测序对20例新诊断NKTCL患者和12例健康供者的外周血单个核细胞(PBMCs)免疫图谱进行了表征,并通过流式细胞术和PrimeFlow验证了结果。
我们在NKTCL中鉴定出一个独特的增殖性NK/T(Proli-NK/T)细胞亚群,其特征为细胞周期相关基因高表达,但缺乏恶性表型。此外,我们观察到总B细胞和经典记忆B细胞减少,并伴有凋亡和细胞分化特征的富集。NK细胞显示HLA II类和活化标志物表达增加,同时与CD4 + T细胞的预测相互作用增强。初始CD4 + T细胞的减少可能意味着其向Th1和Th17细胞的分化偏移,而表达颗粒酶K(GZMK +)的CD8 + 中央记忆T细胞的扩增与干扰素-γ驱动的反应相关。细胞内EBV载量高的患者表现出高细胞毒性CD56 dim _PTPRCAP NK细胞和GZMK + GZMB + CD8 + 效应记忆T细胞的积累,同时伴有记忆B细胞的显著耗竭。这提示细胞内EBV负荷与NKTCL中外周免疫失调之间存在相关性。
In this study, we characterized the immune landscape of peripheral blood mononuclear cells (PBMCs) from 20 newly diagnosed NKTCL patients and 12 healthy donors using single-cell RNA sequencing and confirmed our results through flow cytometry and PrimeFlow.
We identified a distinct proliferative-NK/T (Proli-NK/T) cell subset in NKTCL, characterized by high expression of cell cycle-related genes but lacking a malignant phenotype. Additionally, we observed a reduction in total and classical memory B cells, accompanied by enrichment of apoptosis and cell differentiation signatures. NK cells showed increased expression of HLA class II and activation markers, along with enhanced predicted interactions with CD4 + T cells. The decrease of naive CD4 + T cells might imply their skewed differentiation into Th1 and Th17 cells, while expansion of granzyme K (GZMK + )-expressing CD8 + central memory T cells was associated with interferon-γ-driven responses. Patients with a high intracellular EBV load exhibited accumulation of highly cytotoxic CD56 dim _PTPRCAP NK cells and GZMK + GZMB + CD8 + effector memory T cells, along with a marked depletion of memory B cells. This implies a correlation between intracellular EBV burden and peripheral immune dysregulation in NKTCL.
We have uncovered the dynamic changes in PBMCs of newly diagnosed NK/T cell lymphoma patients and identified specific characteristics in patients with high intracellular EBV levels. Our findings provide new insights into the immunopathogenesis of NKTCL, offering valuable information for immune-based stratification and the development of therapeutic strategies.
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