Abstract：
PD-L1+ exosome have been reported to be a promising prognostic biomarker in various cancers. However, its clinical value in diffuse large B cell lymphoma (DLBCL) has not been defined yet. In this study, a total of 165 plasma samples from 78 patients with DLBCL undergoing standard first-line R-CHOP regimens were collected at three different time points (pretreatment, and after 3 and 6 cycles of R-CHOP) to determine the proportions of PD-L1+ exosomes by flow cytometry. We found that high pretreatment plasma PD-L1+ exosome correlated with indicators of poor clinical outcome that included high Ki-67 expression (P = 0.02), double expressor lymphoma (P = 0.005), immunohistochemical PD-L1+ tumor tissue (P = 0.006), and the baseline maximal standardized uptake values (P = 0.0003). Pretreatment plasma PD-L1+ exosome was an independent factor by multivariate analysis with logistic regression (P = 0.0301). Moreover, the pretreatment PD-L1+ exosome was a strong predictor of final treatment responses of either CR or non-CR by ROC analysis (P < 0.001). PD-L1+ exosome level declined significantly in patients who experienced CR (pretreatment vs. after 3 cycles/after 6 cycles, P < 0.05), but not in the non-CR group. Intriguingly, plasma PD-L1+ exosome after 3 cycles (AUC = 0.857; 95%CI: 0.728-0.939) might represent a more sensitive indicator than radiographic assessment after 3 cycles (AUC = 0.626; 95%CI: 0.477-0.758) for evaluating the therapeutic response of DLBCL patients (P = 0.0136). Our results suggest that plasma PD-L1+ exosomes may represent a new biomarker for the dynamic monitoring of treatment response.
摘要：
PD-L1+外泌体已被报道为各种癌症中的有希望的预后生物标志物。然而,其在弥漫性大B细胞淋巴瘤（DLBCL）中的临床价值尚未确定。在这项研究中,在三个不同的时间点（预处理，并在R-CHOP3和6个周期后）通过流式细胞术确定PD-L1+外泌体的比例。我们发现，高治疗前血浆PD-L1+外泌体与不良临床结局指标相关，包括高Ki-67表达（P=0.02），双表达淋巴瘤（P=0.005），免疫组织化学PD-L1+肿瘤组织（P=0.006），和基线最大标准化摄取值(P=0.0003)。多因素Logistic回归分析显示治疗前血浆PD-L1+外泌体为独立影响因素(P=0.0301)。此外，通过ROC分析,治疗前PD-L1+外泌体是CR或非CR最终治疗反应的强预测因子(P<0.001).经历CR的患者的PD-L1+外泌体水平显着下降（预处理与3个循环后/6个循环后，P<0.05),但不在非CR组中。有趣的是，3个周期后的血浆PD-L1+外泌体(AUC=0.857;95CI:0.728~0.939)对于评估DLBCL患者的治疗反应可能是比3个周期后的影像学评估(AUC=0.626;95CI:0.477~0.758)更敏感的指标(P=0.0136).我们的结果表明，血浆PD-L1+外泌体可能是动态监测治疗反应的新生物标志物。
