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:Mass cytometric analysis of circulating immune landscape in primary central nervous system lymphoma.
PCNSL中的循环免疫景观以单核细胞激活偏斜、T细胞终末耗竭及化疗诱导的效应T细胞扩增为特征。我们的发现将外周免疫特征与肿瘤微环境生物学联系起来。理解这些系统性免疫改变可能为肿瘤免疫逃逸提供见解,并为逆转PCNSL相关免疫抑制提供路线图。
原发性中枢神经系统淋巴瘤(PCNSL)患者的外周免疫特征仍未被充分描述。研究PCNSL中的免疫失调可能有助于阐明潜在的疾病机制。
我们旨在通过质谱流式细胞术,对16名患者和6名健康参与者的免疫细胞特征进行描述,以明确原发性中枢神经系统淋巴瘤(PCNSL)中的循环免疫格局。
患者外周血单个核细胞出现显著改变,包括CD45RO+经典单核细胞扩增(p=0.017)、中间亚群减少(p=0.01)以及CD38表达升高(p<0.001)。终末分化CD8+CD57+ T细胞数量增加(p=0.013),治疗诱导效应T细胞(CD8+ T效应/效应记忆细胞,p<0.05)扩增,并伴随CD38、HLA-DR和CD107a的共上调(p<0.01)。年龄<60岁的患者CD8+初始T细胞频率较高(p<0.05),疾病进展与CD56 bright NK细胞积累相关(p<0.01)。
INTRODUCTION: The peripheral immune profiles of patients with primary central nervous system lymphoma (PCNSL) remain poorly characterized. Investigating immune dysregulation in PCNSL may help elucidate the underlying disease mechanisms. METHODS: We aimed to define the circulating immune landscape in PCNSL by characterizing the immune cell profiles in 16 patients and 6 healthy participants using mass cytometry. RESULTS: Patients exhibited significant alterations in peripheral blood mononuclear cells, including expansion of CD45RO+ classical monocytes (p=0.017), reduced intermediate subsets (p=0.01), and elevated CD38 expression (p<0.001). The number of terminally differentiated CD8+CD57+ T cells increased (p=0.013), and treatment induced effector T cell (CD8+ T effector/effector memory cells, p<0.05) expansion, accompanied by co-upregulation of CD38, HLA-DR, and CD107a (p<0.01). Patients < 60 years had higher frequencies of CD8+ na ve T cells (p<0.05), and progressive disease correlated with CD56 bright NK cell accumulation (p<0.01). CONCLUSION: the circulating immune landscape in PCNSL is characterized by skewed monocyte activation, T cell terminal exhaustion, and chemotherapy-induced effector T cell expansion. Our findings link peripheral immune features to the tumor microenvironment biology. Understanding these systemic immune alterations may provide insights into tumor immune evasion and offer a roadmap for reversing PCNSL-associated immunosuppression.
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