Merlano Marco Carlo, Abbona Andrea, Paccagnella Matteo, Falletta Antonella, Granetto Cristina, Ricci Vincenzo, Fea Elena, Denaro Nerina, Ruatta Fiorella, Merlotti Anna, Bertetto Oscar, Crosetto Nicola, Galizia Danilo, Basiricò Marco, Gammaitoni Loretta, Sangiolo Dario, Aglietta Massimo, Garrone Ornella
Experimental Cell Therapy Lab, Department of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, 10060 Turin, Italy.
Translational Oncology, ARCO Foundation, 12100 Cuneo, Italy.
Vaccines (Basel). 2021 Mar 8;9(3):235. doi: 10.3390/vaccines9030235.
Published data suggest that immunotherapy plays a role even in patients with very advanced tumours. We investigated the immune profile of end-stage cancer patients treated with immunotherapy to identify changes induced by treatment. Breast, colon, renal and prostate cancer patients were eligible. Treatment consisted of metronomic cyclophosphamide, low-dose interleukin-2 (IL-2) and a single radiation shot. A panel of 16 cytokines was assessed using automated ELISA before treatment (T0), after radiation (RT; T1), at cycle 2 (T2) and at disease progression (TPD). Receiving operating characteristic (ROC) analysis was used to identify cytokine cut-off related to overall survival (OS). Principal component analysis (PCA) was used to identify the immune profile correlating better with OS and progression-free survival. Twenty-three patients were enrolled. High IL-2, low IL-8 and CCL-2 correlated with OS. The PCA identified a cluster of patients, with high IL-2, IL-12 and IFN-γ levels at T0 having longer PFS and OS. In all cohorts, IL-2 and IL-5 increased from T0 to T2; a higher CCL-4 level compared to T2 and a higher IL-8 level compared to T0 were found at TPD. The progressive increase of the IL-10 level during treatment negatively correlated with OS. Our data suggested that baseline cytokine levels may predict patients' outcome and that the treatment may affect their kinetic even in end-stage patients. Cytokine profiling of end-stage patients might offer a tool for medical decisions (EUDRACT: 2016-000578-39).
已发表的数据表明，免疫疗法即使在肿瘤非常晚期的患者中也能发挥作用。我们研究了接受免疫疗法治疗的终末期癌症患者的免疫特征，以确定治疗引起的变化。乳腺癌、结肠癌、肾癌和前列腺癌患者符合条件。治疗包括节拍性环磷酰胺、低剂量白细胞介素-2（IL-2）和单次放疗。在治疗前（T0）、放疗后（RT；T1）、第2周期（T2）和疾病进展时（TPD），使用自动酶联免疫吸附测定法评估一组16种细胞因子。采用受试者工作特征（ROC）分析来确定与总生存期（OS）相关的细胞因子临界值。主成分分析（PCA）用于确定与OS和无进展生存期相关性更好的免疫特征。招募了23名患者。高IL-2、低IL-8和CCL-2与OS相关。PCA确定了一组患者，在T0时IL-2、IL-12和IFN-γ水平高的患者具有更长的无进展生存期和总生存期。在所有队列中，IL-2和IL-5从T0到T2升高；在TPD时发现与T2相比CCL-4水平更高，与T0相比IL-8水平更高。治疗期间IL-10水平的逐渐升高与OS呈负相关。我们的数据表明，基线细胞因子水平可能预测患者的预后，并且即使在终末期患者中，治疗也可能影响其动态变化。终末期患者的细胞因子谱分析可能为医疗决策提供一种工具（欧盟临床试验注册号：2016-000578-39）。
