Zizzari Ilaria Grazia, Di Filippo Alessandra, Scirocchi Fabio, Di Pietro Francesca Romana, Rahimi Hassan, Ugolini Alessio, Scagnoli Simone, Vernocchi Pamela, Del Chierico Federica, Putignani Lorenza, Rughetti Aurelia, Marchetti Paolo, Nuti Marianna, Botticelli Andrea, Napoletano Chiara
Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.
Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, "Sapienza" University of Rome, 00189 Rome, Italy.
J Pers Med. 2020 Nov 4;10(4):208. doi: 10.3390/jpm10040208.
Patients with non-small cell lung cancer (NSCLC) have been shown to benefit from the introduction of anti-PD1 treatment. However, not all patients experience tumor regression and durable response. The identification of a string of markers that are direct or indirect indicators of the immune system fitness is needed to choose optimal therapeutic schedules in the management of NSCLC patients. We analyzed 34 immuno-related molecules (14 soluble immune checkpoints, 17 cytokines/chemokines, 3 adhesion molecules) released in the serum of 22 NSCLC patients under Nivolumab treatment and the gut metabolomic profile at baseline. These parameters were correlated with performance status (PS) and/or response to treatment. Nivolumab affected the release of soluble immune checkpoints (sICs). Patients with a better clinical outcome and with an optimal PS (PS = 0) showed a decreased level of PD1 and maintained low levels of several sICs at first clinical evaluation. Low levels of PDL1, PDL2, Tim3, CD137 and BTLA4 were also correlated with a long response to treatment. Moreover, responding patients showed a high proportion of eubiosis-associated gut metabolites. In this exploratory study, we propose a combination of immunological and clinical parameters (sICs, PS and gut metabolites) for the identification of patients more suitable for Nivolumab treatment. This string of parameters validated in a network analysis on a larger cohort of patients could help oncologists to improve their decision-making in an NSCLC setting.
非小细胞肺癌（NSCLC）患者已被证明可从抗PD1治疗中获益。然而，并非所有患者都能出现肿瘤消退和持久反应。在NSCLC患者的管理中，需要识别一系列作为免疫系统健康直接或间接指标的标志物，以选择最佳治疗方案。我们分析了22例接受纳武单抗治疗的NSCLC患者血清中释放的34种免疫相关分子（14种可溶性免疫检查点、17种细胞因子/趋化因子、3种黏附分子）以及基线时的肠道代谢组学特征。这些参数与体能状态（PS）和/或治疗反应相关。纳武单抗影响可溶性免疫检查点（sICs）的释放。临床结局较好且PS最佳（PS = 0）的患者在首次临床评估时PD1水平降低，且几种sICs维持在低水平。PDL1、PDL2、Tim3、CD137和BTLA4水平较低也与长期治疗反应相关。此外，有反应的患者显示出与有益菌相关的肠道代谢产物比例较高。在这项探索性研究中，我们提出将免疫和临床参数（sICs、PS和肠道代谢产物）相结合，以识别更适合纳武单抗治疗的患者。在更大规模患者队列的网络分析中验证的这一系列参数，可帮助肿瘤学家在NSCLC治疗中改善决策。
