PD-1 blocking agents, such as nivolumab, have demonstrated clear anti-tumor effects and clinical benefits in a subset of patients with advanced malignancies. Nonetheless, more efforts are needed to identify reliable biomarkers for outcome, to correctly select patients who will benefit from anti-PD-1 treatment. The aim of this study was to investigate the role of peripheral CD8+T cells expressing CD73, involved in the generation of the immune suppressive molecule adenosine, in predicting outcome after nivolumab treatment in advanced melanoma patients. PBMCs from 100 melanoma patients treated with nivolumab were collected at National Cancer Institute “G. Pascale” of Naples. Frequencies of CD8+ lymphocytes phenotypes were assessed by flow cytometry at baseline before nivolumab treatment, along with clinical characteristics and blood count parameters. Healthy controls (n = 20) were also analysed. Percentages of baseline T cells expressing PD-1 and CD73 were correlated with outcome after nivolumab treatment. Melanoma patients presented a lower frequency of total circulating CD8+ lymphocytes than control subjects (p = 0.008). Patients with low baseline percentage of circulating CD8+PD-1+CD73+ lymphocytes (< 2.3%) had better survival (22.4 months vs 6.9 months, p = 0.001). Patients (39%) with clinical benefit from nivolumab therapy presented a significantly lower frequency of circulating CD8+PD-1+CD73+ lymphocytes than patients who progressed to nivolumab treatment (p = 0.02). Our observations suggest that baseline CD73 expression on circulating CD8+PD-1+ lymphocytes appear a promising biomarker of response to anti-PD-1 treatment in melanoma patients. Further investigations are needed for validation and for clarifying its role as prognostic or predictive marker.

中文翻译：

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循环 CD8+CD73+T 细胞的频率与纳武单抗治疗的黑色素瘤患者的生存相关。


PD-1 阻断剂（例如纳武单抗）已在部分晚期恶性肿瘤患者中表现出明显的抗肿瘤作用和临床益处。尽管如此，仍需要付出更多努力来确定可靠的生物标志物，以正确选择将从抗 PD-1 治疗中受益的患者。本研究的目的是调查表达 CD73 的外周 CD8+T 细胞（参与免疫抑制分子腺苷的生成）在预测晚期黑色素瘤患者纳武单抗治疗后的结果中的作用。美国国家癌症研究所“G.那不勒斯的帕斯卡尔。在纳武单抗治疗前，通过流式细胞术评估基线时 CD8+ 淋巴细胞表型的频率以及临床特征和血细胞计数参数。还对健康对照 (n = 20) 进行了分析。表达 PD-1 和 CD73 的基线 T 细胞的百分比与纳武单抗治疗后的结果相关。黑色素瘤患者的总循环 CD8+ 淋巴细胞频率低于对照组 (p = 0.008)。循环 CD8+PD-1+CD73+ 淋巴细胞基线百分比较低 (< 2.3%) 的患者生存期较好（22.4 个月 vs 6.9 个月，p = 0.001）。从纳武单抗治疗中获得临床获益的患者 (39%) 的循环 CD8+PD-1+CD73+ 淋巴细胞频率明显低于进展至纳武单抗治疗的患者 (p = 0.02)。我们的观察表明，循环 CD8+PD-1+ 淋巴细胞上的基线 CD73 表达似乎是黑色素瘤患者抗 PD-1 治疗反应的有希望的生物标志物。需要进一步研究来验证并阐明其作为预后或预测标记的作用。