CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes Université, Nantes, France.
Immunology Graft Oncology, Labex IGO, Nantes, France.
Mol Oncol. 2022 Oct;16(20):3606-3619. doi: 10.1002/1878-0261.13310. Epub 2022 Sep 10.
Malignant pleural mesothelioma (MPM) is an aggressive cancer mainly related to asbestos exposure. Despite recent therapeutic advances, notably immunotherapies, the benefit remains limited and restricted to a small percentage of patients. Thus, a better understanding of the disease is needed to identify new therapeutic strategies. Recently, interleukin 7 receptor (IL-7R) has been described as being expressed by MPM cells and associated with poorer patient survival. Thus, the aim of this work was to study the IL-7R/IL-7 pathway in MPM using patient samples. We found that, although more than 40% of MPM cells expressed IL-7R, IL-7 had no effect on their intracellular signaling. Accordingly, the addition of IL-7 to the culture medium did not affect MPM cell growth. Using The Cancer Genome Atlas (TCGA) database, we showed that high IL7 gene expression in MPM tumors was associated with a higher overall patient survival and an induction of genes involved in the immune response. In pleural effusions (PEs), we found that IL-7 concentration was not a good diagnostic biomarker. However, we observed that high IL-7 levels in PEs were associated with shorter survival of MPM patients, but not of lung cancer patients. The prognostic value of IL-7 was also conserved when only patients with epithelioid mesothelioma, the most common histological type of MPM, were analyzed. Taken together, our study suggests that, although the IL-7R/IL-7 signaling pathway is not functional in MPM cells, IL-7 expression in PEs may have prognostic value in MPM patients.
恶性胸膜间皮瘤(MPM)是一种主要与石棉暴露有关的侵袭性癌症。尽管最近有治疗进展,特别是免疫疗法,但获益仍然有限,仅限于一小部分患者。因此,需要更好地了解疾病,以确定新的治疗策略。最近,白细胞介素 7 受体(IL-7R)被描述为 MPM 细胞表达,并与患者生存较差相关。因此,本研究旨在使用患者样本研究 MPM 中的 IL-7R/IL-7 通路。我们发现,尽管超过 40%的 MPM 细胞表达 IL-7R,但 IL-7 对其细胞内信号没有影响。因此,向培养基中添加 IL-7 不会影响 MPM 细胞的生长。使用癌症基因组图谱(TCGA)数据库,我们表明 MPM 肿瘤中高 IL7 基因表达与患者总体生存率提高和参与免疫反应的基因诱导相关。在胸腔积液(PEs)中,我们发现 IL-7 浓度不是一个很好的诊断生物标志物。然而,我们观察到 PEs 中高 IL-7 水平与 MPM 患者的生存时间较短相关,但与肺癌患者无关。当仅分析最常见的 MPM 组织学类型上皮样间皮瘤患者时,IL-7 的预后价值仍然保持不变。综上所述,我们的研究表明,尽管 IL-7R/IL-7 信号通路在 MPM 细胞中没有功能,但 PEs 中 IL-7 的表达可能对 MPM 患者具有预后价值。