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白细胞介素-7 在恶性间皮瘤中表达,并具有预后价值。

IL-7 is expressed in malignant mesothelioma and has a prognostic value.

机构信息

CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes Université, Nantes, France.

Immunology Graft Oncology, Labex IGO, Nantes, France.

出版信息

Mol Oncol. 2022 Oct;16(20):3606-3619. doi: 10.1002/1878-0261.13310. Epub 2022 Sep 10.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/385c/9580880/250abd6328ae/MOL2-16-3606-g004.jpg

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