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:A novel model for predicting prognosis and response to immunotherapy in nasopharyngeal carcinoma patients.
在训练队列(n = 130)中,于基于ICIs的治疗前测定了淋巴细胞亚群、生化指标和血常规的绝对值。
鼻咽癌(NPC)患者免疫检查点抑制剂(ICIs)应答的血液生物标志物尚缺乏,因此有必要识别生物标志物以筛选最可能或最不可能从ICIs中获益的NPC患者。在训练队列(n = 130)中,于基于ICIs的治疗前测定淋巴细胞亚群绝对值、生化指标和血常规。随后,开发最小绝对收缩和选择算子(Lasso)Cox回归分析以构建预测模型。使用一致性指数(C-index)将该预测模型的性能与TNM分期、治疗和Epstein-Barr病毒(EBV)DNA进行比较。通过Kaplan-Meier(K-M)生存曲线估计无进展生存期(PFS)。另外63例患者用于验证队列。该新模型由组织学亚型、CD19 + B细胞、自然杀伤(NK)细胞、调节性T细胞、红细胞(RBC)、AST/ALT比值(SLR)、载脂蛋白B(Apo B)和乳酸脱氢酶(LDH)组成。该模型的C-index在训练队列中为0.784,在验证队列中为0.735。K-M生存曲线显示,与低风险组相比,高风险评分患者的PFS更短。在预测免疫治疗应答方面,该模型的受试者工作特征(ROC)、决策曲线分析(DCA)、净重分类改善指数(NRI)和综合判别改善指数(IDI)显示出优于EBV DNA的预测能力。在本研究中,我们构建了一种用于NPC患者预后预测和免疫治疗反应预测的新模型,这可能为选择那些可能从抗PD-1治疗中获得持久临床获益的患者提供临床帮助。
Blood-based biomarkers of immune checkpoint inhibitors (ICIs) response in patients with nasopharyngeal carcinoma (NPC) are lacking, so it is necessary to identify biomarkers to select NPC patients who will benefit most or least from ICIs. The absolute values of lymphocyte subpopulations, biochemical indexes, and blood routine tests were determined before ICIs-based treatments in the training cohort (n = 130). Then, the least absolute shrinkage and selection operator (Lasso) Cox regression analysis was developed to construct a prediction model. The performances of the prediction model were compared to TNM stage, treatment, and Epstein-Barr virus (EBV) DNA using the concordance index (C-index). Progression-free survival (PFS) was estimated by Kaplan-Meier (K-M) survival curve. Other 63 patients were used for validation cohort. The novel model composed of histologic subtypes, CD19 + B cells, natural killer (NK) cells, regulatory T cells, red blood cells (RBC), AST/ALT ratio (SLR), apolipoprotein B (Apo B), and lactic dehydrogenase (LDH). The C-index of this model was 0.784 in the training cohort and 0.735 in the validation cohort. K-M survival curve showed patients with high-risk scores had shorter PFS compared to the low-risk groups. For predicting immune therapy responses, the receiver operating characteristic (ROC), decision curve analysis (DCA), net reclassifcation improvement index (NRI) and integrated discrimination improvement index (IDI) of this model showed better predictive ability compared to EBV DNA. In this study, we constructed a novel model for prognostic prediction and immunotherapeutic response prediction in NPC patients, which may provide clinical assistance in selecting those patients who are likely to gain long-lasting clinical benefits to anti-PD-1 therapy.
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