Five-year progression-free survival and overall survival based on CD73 and CD155 expression in resected epithelial malignant pleural mesothelioma: a retrospective single-centre study

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour requiring multidisciplinary treatment. Identifying prognostic biomarkers could improve treatment planning and patient outcomes. CD73 and CD155 are immunomodulatory molecules involved in immune evasion and tumour progression in various cancers; however, their roles in MPM remain unclear. Therefore, this study aimed to investigate the association between CD73 and CD155 expression in resected epithelial MPM specimens and their impact on 5-year progression-free survival (PFS) and 5-year overall survival (OS). Methods: This single-centre retrospective study included 43 consecutive patients with epithelial MPM who underwent curative-intent surgery, with or without chemotherapy and immune checkpoint inhibitor (ICI) treatment, at our institution between January 1, 2013 and December 31, 2020. Immunohistochemical staining for CD73 and CD155 was performed on surgical specimens, and HALO-AI pathology software was used for quantitative analysis. Receiver operating characteristic (ROC) curve analysis determined cutoff values for CD73/CD155 positivity. Patients were categorised into CD73+/CD155+ and non-CD73+/CD155+ groups and survival outcomes (5-year PFS and 5-year OS) were analysed using Kaplan–Meier curves. Cox proportional hazards regression was used for univariate and multivariate analyses to identify independent prognostic factors. Results: Among 35 evaluable cases, patients with CD73+/CD155+ tumours had significantly improved 5-year PFS compared with those with non-CD73+/CD155+ tumours (64.8% vs. 10.8%, p=0.017), though OS differences were not significant (p=0.376). Among CD73+/CD155+ patients, those who underwent postoperative pleurodesis with OK432 demonstrated significantly higher PFS (83.3% vs. 33.3%, p=0.043), suggesting a potential therapeutic benefit. In contrast, in non-CD73+/CD155+ cases, postoperative chemotherapy significantly improved PFS (p=0.03). Multivariate analysis revealed non-CD73+/CD155+ expression and lack of postoperative chemotherapy as independent predictors of disease progression (HR 6.555, p=0.008) and mortality (HR 5.835, p=0.006). Among recurrent cases, patients treated with ICIs had significantly improved OS (p=0.001), highlighting the potential role of immunotherapy in this subgroup. Conclusions: CD73 and CD155 expression patterns may serve as prognostic biomarkers in epithelial MPM. CD73+/CD155+ tumours appear to benefit from pleurodesis with OK432, while non-CD73+/CD155+ tumours may be more responsive to postoperative chemotherapy. These findings suggest that CD73/CD155 status could guide personalised treatment strategies in MPM, warranting further validation in larger cohorts.