CD70 expression correlates with a worse prognosis in malignant pleural mesothelioma patients via immune evasion and enhanced invasiveness

作者：Shingo Inaguma, Jerzy P. Lasota, Piotr Czapiewski, Renata Langfort, Janusz Ryś, Joanna Szpor, Piotr Waloszczyk, Krzysztof Okoń, Wojciech Biernat, David S. Schrump, Raffit Hassan, Kenji Kasai, Markku Miettinen, Hiroshi Ikeda · 发表于：The Journal of Pathology · 年份：2019 · DOI：10.1002/path.5361 · 被引用次数：70 · 研究领域：Occupational and environmental lung diseases、Pleural and Pulmonary Diseases、Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis

Abstract Diffuse malignant mesothelioma of the pleura (MPM) is a highly aggressive tumour that typically is associated with short survival. CD70 and CD27 belong to the tumour necrosis factor (TNF) and the TNF receptor (TNFR) superfamily, respectively. Under physiological conditions, the tightly regulated interaction between CD70 and CD27 plays a co‐stimulatory role in promoting T‐cell expansion and differentiation through the NFκB pathway. Aberrantly high CD70 expression has been documented in haematological and solid malignancies in association with immune evasion in malignant cells. In this study, 172 well‐characterised primary diffuse MPM tumours including epithelioid ( n = 145), biphasic ( n = 15), and sarcomatoid ( n = 12) histotypes were evaluated immunohistochemically for CD70, CD27, CD3, CD4, CD8, CD56, PDCD1 (PD‐1), and FOXP3 expression. Twenty per cent (34/172) of the mesothelioma cells expressed CD70 on the cell membrane. Overall survival was significantly decreased in the cohort of patients with CD70‐expressing tumour cells ( p < 0.01). Patients with MPM containing a higher number of CD3 + ( p < 0.01), CD4 + ( p < 0.01), CD8 + ( p < 0.01), or FOXP3 + ( p < 0.01) tumour‐infiltrating lymphoid cells (TILs) showed significantly worse clinical outcomes. As potential independent risk factors for MPM patients, multivariate Cox proportional hazards regression analysis revealed CD70 expression on mesothelioma cells [hazard ratio (HR) 2.25; p = 0.010], higher FOXP3 + TILs (...