Tracking the evolution of circulating exosomal-PD-L1 to monitor melanoma patients
Tracking the evolution of circulating exosomal-PD-L1 to monitor melanoma patients
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DOI：
10.1080/20013078.2019.1710899
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发表时间：
2020-01-01
影响因子：
16
通讯作者：
Gobbo, Jessica
中科院分区：
文献类型：
--
作者：
Cordonnier, Marine;Nardin, Charlee;Gobbo, Jessica
在免疫治疗的时代，迫切需要在临床实践中使用循环生物标记物，以促进个性化治疗和预测治疗反应。我们进行了一项前瞻性研究，以评估循环胞外体-PD-L1在黑色素瘤患者随访中的有效性。我们用酶联免疫吸附试验研究了100例黑色素瘤患者外体-PD-L1的动态变化。我们发现PD-L1是由黑色素瘤细胞通过外切体分泌的。携带PD-L1的外切体具有免疫抑制特性，因为它们与其来源的癌细胞一样有效地抑制T细胞的激活。在黑色素瘤患者血浆中，外切体的PD-L1水平(n=30，中位数64.26 pg/m L)显著高于可溶性PD-L1(n=30，0.1pg/m L)。此外，所有患者都检测到胞外体PD-L1，而只有67%的肿瘤活检组织PD-L1阳性。虽然基线Exosomal-PD-L1水平与临床病理特征无关，但它们在治疗后的变化(Delta ExoPD-L1)与肿瘤对治疗的反应有关。Delta ExoPD-L1的分界值为>；100，对疾病进展的敏感性为83%，特异性为70%，阳性预测值为91%，阴性预测值为54%。在总体生存期和无进展生存期方面，两组患者在统计学上不同，使用截断点可以分层。在肿瘤活检中，循环外切体中PD-L1的水平似乎比PD-L1的表达更可靠。监测循环胞外体-PD-L1可能有助于预测肿瘤对治疗的反应和临床结果。
In the era of immunotherapies there is an urgent need to implement the use of circulating biomarkers in clinical practice to facilitate personalized therapy and to predict treatment response. We conducted a prospective study to evaluate the usefulness of circulating exosomal-PD-L1 in melanoma patients' follow-up. We studied the dynamics of exosomal-PD-L1 from 100 melanoma patients by using an enzyme-linked immunosorbent assay. We found that PD-L1 was secreted through exosomes by melanoma cells. Exosomes carrying PD-L1 had immunosuppressive properties since they were as efficient as the cancer cell from which they derive at inhibiting T-cell activation. In plasma from melanoma patients, the level of PD-L1 (n= 30, median 64.26 pg/mL) was significantly higher in exosomes compared to soluble PD-L1 (n= 30, 0.1 pg/mL). Furthermore, exosomal-PD-L1 was detected in all patients whereas only 67% of tumour biopsies were PD-L1 positive. Although baseline exosomal-PD-L1 levels were not associated with clinic-pathologic characteristics, their variations after the cures (Delta ExoPD-L1) correlated with the tumour response to treatment. A Delta ExoPD-L1 cut-off of> 100 was defined, yielding an 83% sensitivity, a 70% specificity, a 91% positive predictive value and 54% negative predictive values for disease progression. The use of the cut-off allowed stratification in two groups of patients statistically different concerning overall survival and progression-free survival. PD-L1 levels in circulating exosomes seem to be a more reliable marker than PD-L1 expression in tumour biopsies. Monitoring of circulating exosomal-PD-L1 may be useful to predict the tumour response to treatment and clinical outcome.