Impact of CD73/CD155 Expression on Survival in Resected Epithelial Pleural Mesothelioma: A Retrospective Single-center Study

<h3>Background/Aim:</h3> While CD73 and CD155 are implicated in immune evasion and tumor progression, their roles in pleural mesothelioma (PM) remain unclear. Therefore, we investigated the association between CD73 and CD155 expression in resected epithelial PM specimens and explored their impact on 5-year progression-free survival (PFS) and 5-year overall survival (OS). <h3>Patients and Methods:</h3> This single-center retrospective study enrolled 43 patients with epithelial PM who underwent curative-intent surgery, with/without chemotherapy and immune checkpoint inhibitor (ICI) treatment, between January 2013 and December 2020. HALO-AI pathology software was used to quantify CD73 and CD155 expression following immunohistochemical staining. Cutoff values for CD73/CD155 positivity were determined using receiver operating characteristic curves. Patients were categorized into CD73+/CD155+ and non-CD73+/CD155+ groups, and survival outcomes were analyzed using Kaplan-Meier curves and Cox proportional hazards regression. <h3>Results:</h3> Among 35 cases, patients with CD73+/CD155+ tumors exhibited significantly improved 5-year PFS compared with those with non-CD73+/CD155+ tumors (64.8% <i>vs.</i> 10.8%, <i>p</i>=0.017); however, OS differences were not significant (<i>p</i>=0.376). Among CD73+/CD155+ cases, postoperative pleurodesis with OK432 was associated with improved PFS (83.3% <i>vs.</i> 33.3%, <i>p</i>=0.03). Among non-CD73+/CD155+ cases, postoperative chemotherapy significantly improved PFS (<i>p</i>&lt;0.001). Univariate analysis identified non-CD73+/CD155+ expression as an independent predictor of disease progression [hazard ratio (HR)=0.2546, <i>p</i>=0.02933]. Among recurrent cases, patients treated with ICIs exhibited significantly improved OS (<i>p</i>=0.001), highlighting the potential of immunotherapy. <h3>Conclusion:</h3> CD155 may serve as a poor prognostic factor in mesothelioma and represents the first immunohistochemical evaluation of this marker. Although CD73 and CD155 co-expression were initially predicted to indicate poor prognosis, findings were unexpected, likely due to inability to establish an optimal cutoff value given variations in patient demographics, disease stage, and treatment approaches.