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:CD16+ as predictive marker for early relapse in aggressive B-NHL/DLBCL patients.
我们对46例患者的血液样本进行了表型和功能分析,重点关注CD16+ NK细胞、CD16+ T细胞和CD16+单核细胞。
评估侵袭性非霍奇金B细胞淋巴瘤患者的预后主要依赖于临床风险评分(IPI)。标准一线治疗基于利妥昔单抗联合化疗免疫治疗,利妥昔单抗介导CD16依赖性抗体依赖性细胞毒性(ADCC)。我们对46例患者的血液样本进行了表型和功能分析,重点关注CD16+ NK细胞、CD16+ T细胞和CD16+单核细胞。Kaplan-Meier生存曲线显示,诊断时CD16+ T细胞大于1.6%的患者具有更优的无进展生存期(PFS)(p = 0.02;HR = 0.13(0.007-0.67)),而CD16+单核细胞大于10.0%的患者PFS较差(p = 0.0003;HR = 16.0(3.1-291.9))。出乎意料的是,未发现与NK细胞的相关性。CD16+单核细胞> 10.0%时增加的复发风险可被同时出现的CD16+ T细胞> 1.6%所逆转。CD16+ T细胞出乎意料的强保护功能可能由其高抗体依赖性细胞毒性所解释,这一点通过实时杀伤试验和单细胞成像进行了定量。CD16+单核细胞(> 10%)和CD16+ T细胞(< 1.6%)的联合分析提供了一个强效模型,Harrell's C指数为0.80,即使在我们46例患者的样本量下,检验效能也高达0.996。因此,初始血液分析中的CD16评估是早期复发预测的精确标志物。
Assessing the prognosis of patients with aggressive non-Hodgkin B cell lymphoma mainly relies on a clinical risk score (IPI). Standard first-line therapies are based on a chemo-immunotherapy with rituximab, which mediates CD16-dependent antibody-dependent cellular cytotoxicity (ADCC). We phenotypically and functionally analyzed blood samples from 46 patients focusing on CD16+ NK cells, CD16+ T cells and CD16+ monocytes. Kaplan-Meier survival curves show a superior progression-free survival (PFS) for patients having more than 1.6% CD16+ T cells (p = 0.02; HR = 0.13 (0.007-0.67)) but an inferior PFS having more than 10.0% CD16+ monocytes (p = 0.0003; HR = 16.0 (3.1-291.9)) at diagnosis. Surprisingly, no correlation with NK cells was found. The increased risk of relapse in the presence of > 10.0% CD16+ monocytes is reversed by the simultaneous occurrence of > 1.6% CD16+ T cells. The unexpectedly strong protective function of CD16+ T cells could be explained by their high antibody-dependent cellular cytotoxicity as quantified by real-time killing assays and single-cell imaging. The combined analysis of CD16+ monocytes (> 10%) and CD16+ T cells (< 1.6%) provided a strong model with a Harrell's C index of 0.80 and a very strong power of 0.996 even with our sample size of 46 patients. CD16 assessment in the initial blood analysis is thus a precise marker for early relapse prediction.
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