Nardone Valerio, Giannicola Rocco, Giannarelli Diana, Saladino Rita Emilena, Azzarello Domenico, Romeo Caterina, Bianco Giovanna, Rizzo Maria Rosaria, Di Meo Irene, Nesci Antonio, Pastina Pierpaolo, Falzea Antonia Consuelo, Caracciolo Daniele, Reginelli Alfonso, Caraglia Michele, Luce Amalia, Mutti Luciano, Giordano Antonio, Cappabianca Salvatore, Pirtoli Luigi, Barbieri Vito, Tassone Pierfrancesco, Tagliaferri Pierosandro, Correale Pierpaolo
Department of Precision Medicine, University of Campania "L. Vanvitelli", 80138 Naples, Italy.
Medical Oncology Unit, Grand Metropolitan Hospital "Bianchi-Melacrino-Morelli", 89124 Reggio Calabria, Italy.
Life (Basel). 2021 Nov 15;11(11):1235. doi: 10.3390/life11111235.
An immune checkpoint blockade with mAbs to PD-1 and PD-L1 is an expanding therapeutic option for mNSCLC patients. This treatment strategy is based on the use of mAbs able to restore the anti-tumor activity of intratumoral T cells inhibited by PD-1 binding to PD-L1/2 on tumor and inflammatory cells. It has been speculated that a chronic status of systemic inflammation as well as the immunosenescence physiologically occurring in elderly patients may affect the efficacy of the treatment and the occurrence of irAEs. We performed a multi-institutional retrospective study aimed at evaluating the effects of these mAbs (nivolumab or atezolizumab) in 117 mNSCLC patients younger (90 cases) and older (27 cases) than 75 years in correlation with multiple inflammatory parameters (NLR, CRP, ESR, LDH and PCT). No differences were observed when the cohorts were compared in terms of the frequency of PFS, OS, inflammatory markers and immune-related adverse events (irAEs). Similarly, the occurrence of irAEs was strictly correlated with a prolonged OS survival in both groups. On the contrary, a negative correlation between the high baseline levels of inflammatory markers and OS could be demonstrated in the younger cohort only. Overall, PD-1/PD-L1-blocking mAbs were equally effective in young and elderly mNSCLC patients; however, the detrimental influence of a systemic inflammation at the baseline was only observed in young patients, suggesting different aging-related inflammation immunoregulative effects.
使用抗PD-1和抗PD-L1单克隆抗体进行免疫检查点阻断是晚期非小细胞肺癌（mNSCLC）患者不断增加的一种治疗选择。这种治疗策略基于使用单克隆抗体，能够恢复肿瘤内T细胞的抗肿瘤活性，这些T细胞因PD-1与肿瘤细胞和炎性细胞上的PD-L1/2结合而受到抑制。据推测，全身炎症的慢性状态以及老年患者生理上发生的免疫衰老可能会影响治疗效果和免疫相关不良反应（irAE）的发生。我们进行了一项多机构回顾性研究，旨在评估这些单克隆抗体（纳武单抗或阿特珠单抗）对117例年龄小于75岁（90例）和大于75岁（27例）的mNSCLC患者的影响，并与多个炎症参数（中性粒细胞与淋巴细胞比值、C反应蛋白、红细胞沉降率、乳酸脱氢酶和降钙素原）进行相关性分析。在比较两组患者的无进展生存期、总生存期、炎症标志物和免疫相关不良事件（irAE）的发生率时，未观察到差异。同样，两组中irAE的发生都与总生存期的延长密切相关。相反，仅在年轻队列中可以证明炎症标志物的高基线水平与总生存期之间存在负相关。总体而言，抗PD-1/PD-L1单克隆抗体在年轻和老年mNSCLC患者中同样有效；然而，仅在年轻患者中观察到基线时全身炎症的有害影响，这表明与衰老相关的炎症免疫调节作用不同。
