Sciammarella Concetta, Luce Amalia, Riccardi Ferdinando, Mocerino Carmela, Modica Roberta, Berretta Massimiliano, Misso Gabriella, Cossu Alessia Maria, Colao Annamaria, Vitale Giovanni, Necas Alois, Fedacko Jan, Galdiero Marilena, Correale Pierpaolo, Faggiano Antongiulio, Caraglia Michele, Capasso Anna, Grimaldi Anna
Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.
Department of Clinical Medicine and Surgery, University "Federico II" of Naples, Naples, Italy.
Front Oncol. 2020 Jul 7;10:1047. doi: 10.3389/fonc.2020.01047. eCollection 2020.
Somatostatin analogs mantain their major role in the treatment of patients with advanced neuroendocrine tumors (NETs) and have multiple modulatory effects on the immune system. Here, we evaluated the effects of lanreotide treatment on expression of Th1, Th2 cytokine patterns in serum of patients with NETs and in bronchial and pancreatic NET cell lines. Our results showed that lanreotide treatment promoted a Th1 cytotoxic immune-phenotype in patients with NETs originated by intestinal sites. Similar results were obtained also where lanreotide induced expression of Th1 cytokines only in pancreatic and not in bronchial-derived NET cell lines. It seems, therefore, that cytokinomics can represent a useful tool for the identification of tumor biomarkers for the early diagnosis and evaluation of the response to therapy in NET patients. To avoid the drug-resistance induced by everolimus (mTOR inhibitor), we made the pancreatic NET cell line resistant to this drug. After treatment with lanreotide we found that the drug reduced its viability compared to that of sensitive cells. These data may have direct implications in design of future translation combination trial on NET patients.
生长抑素类似物在晚期神经内分泌肿瘤（NETs）患者的治疗中仍发挥着主要作用，并且对免疫系统具有多种调节作用。在此，我们评估了兰瑞肽治疗对NETs患者血清以及支气管和胰腺NET细胞系中Th1、Th2细胞因子模式表达的影响。我们的结果表明，兰瑞肽治疗可促进起源于肠道部位的NETs患者出现Th1细胞毒性免疫表型。在兰瑞肽仅诱导胰腺而非支气管来源的NET细胞系中Th1细胞因子表达的情况下，也获得了类似结果。因此，细胞因子组学似乎可以成为识别肿瘤生物标志物的有用工具，用于NET患者的早期诊断和治疗反应评估。为避免依维莫司（一种mTOR抑制剂）诱导的耐药性，我们使胰腺NET细胞系对该药物产生抗性。用兰瑞肽治疗后，我们发现与敏感细胞相比，该药物降低了其活力。这些数据可能对未来NET患者的转化联合试验设计具有直接影响。
