Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Biotherapies Unit, IRCCS Ospedale Policlinico San Martino, Largo Benzi 10, 16132, Genoa, Italy.
Cancer Immunol Immunother. 2021 Nov;70(11):3349-3355. doi: 10.1007/s00262-021-02965-w. Epub 2021 May 18.
Literature reports suggest that the host immune system may control Malignant Pleural Mesothelioma (MPM) growth, although its activity is limited by regulatory mechanisms. In this retrospective study, we analyzed the levels of pro-inflammatory (IL-1, IL-6, TNF), immune-regulatory (IL-10) and Th1/CTL-related cytokines (IL-12p70, IFN-γ) in the pleural exudate and their relationship with overall survival (OS) in MPM.
Cytokines were quantified by multiplexed immunoassay. Concentrations were dichotomized with respect to the median value. Correlation between cytokine level and OS was assessed using univariate (Kaplan-Meier curves) and multivariate (Cox regression) analyses.
Regarding outcome, tumor histology, therapies undergone and IFN-γ were independent prognostic factors of OS in a 72 MPM training cohort. Notably, high concentrations of IFN-γ halved death probability (HR of high vs low IFN-γ concentration = 0.491, 95%CI 0.3-0.8, p = 0.007). Also in patients with epithelioid histology and those receiving at least one line of therapy, high IFN-γ level was an independent factor predictive of OS (HR of high vs low IFN-γ concentration were 0.497, p = 0.007 and 0.324, p = 0.006, respectively). However, these data were not confirmed in a 77 MPM validation cohort, possibly due to the low IFN-γ levels encountered in this population, and the heterogeneous distribution of disease stages between the training and the validation cohorts. None of the other cytokines showed any effect on survival.
High level of IFN-γ in pleural effusion may be associated with better survival in MPM patients and potentially serve as a prognostic biomarker. Larger prospective studies are needed to ascertain this hypothesis.
文献报道表明，宿主免疫系统可能控制恶性胸膜间皮瘤（MPM）的生长，但其活性受到调节机制的限制。在这项回顾性研究中，我们分析了胸腔渗出液中促炎（IL-1、IL-6、TNF）、免疫调节（IL-10）和 Th1/CTL 相关细胞因子（IL-12p70、IFN-γ）的水平及其与 MPM 总生存（OS）的关系。
通过多重免疫测定法定量细胞因子。根据中位数将浓度分为两组。使用单变量（Kaplan-Meier 曲线）和多变量（Cox 回归）分析评估细胞因子水平与 OS 之间的相关性。
关于结果，肿瘤组织学、所接受的治疗和 IFN-γ是 72 名 MPM 训练队列中 OS 的独立预后因素。值得注意的是，高浓度 IFN-γ使死亡概率减半（高浓度 IFN-γ与低浓度 IFN-γ浓度的 HR=0.491，95%CI 0.3-0.8，p=0.007）。在具有上皮样组织学的患者和至少接受一线治疗的患者中，高 IFN-γ水平也是 OS 的独立预测因素（高浓度 IFN-γ与低浓度 IFN-γ浓度的 HR 分别为 0.497，p=0.007 和 0.324，p=0.006）。然而，这些数据在 77 名 MPM 验证队列中并未得到证实，这可能是由于该人群中 IFN-γ 水平较低，以及训练队列和验证队列之间疾病分期分布不均所致。其他细胞因子均未显示对生存有任何影响。
胸腔渗出液中高水平的 IFN-γ可能与 MPM 患者的生存改善相关，并可能作为一种预后生物标志物。需要更大规模的前瞻性研究来证实这一假设。
