Prevalence and Clinical Association of CD276 (B7-H3) Expression in Pleural Mesothelioma: Results From the European Thoracic Platform Mesoscape Project.

IF 5.3 2区医学 Q1 ONCOLOGY JCO precision oncology Pub Date : 2025-02-01 Epub Date: 2025-02-12 DOI:10.1200/PO-24-00675

Martina Haberecker, Jan H Rüschoff, Charitini Andriakopoulou, Steven G Gray, Kristiaan Nackaerts, Marc De Perrot, Luka Brcic, Ernest Nadal, Sotirios Tsimpoukis, Luca Ampollini, Joachim G Aerts, Michaela B Kirschner, Kim Monkhorst, Birgit Weynand, Fatemeh Bavaghar-Zaeimi, Miroslav Samarzija, Roger Llatjos, Stephen P Finn, Enrico Silini, Jan Von Der Thüsen, Patrick Vagenknecht, Zoi Tsourti, Keith M Kerr, Roswitha Kammler, Solange Peters, Paul Baas, Isabelle Opitz, Rolf A Stahel, Alessandra Curioni-Fontecedro

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Abstract

Purpose: CD276 (B7-H3) is an immunoregulatory protein that plays an important role in the inhibition of T-cell function. CD276 is overexpressed on a variety of human solid cancer cells with limited expression in normal tissues, making it an appealing target for innovative cancer immunotherapy approaches. Pleural mesothelioma (PM) is a highly aggressive disease with a need for new treatment options. Our objective was to investigate the expression of CD276 in the multicenter PM cohort of the European Thoracic Oncology Platform Mesoscape project and correlate the results with annotated clinical data.

Materials and methods: Using tissue microarrays (TMAs), the expression of CD276, assessed using a semiquantitative aggregate H-score method on the membrane (and secondarily in the cytoplasm), was correlated with clinicopathologic characteristics and survival outcome.

Results: CD276 immunohistochemistry results were available for 353 patients, with mostly epithelioid histology (71%). Membranous CD276 expression was present in 86%. High membranous CD276 expression (H-score ≥the median H-score of 120) was significantly more common in females (P = .0029; 71% v 47%) and in epithelioid histology (P < .001; 59% v 29%), whereas no significant association in clinical outcome (overall survival [OS]/progression-free survival) was found. Cross-validation of the TMA method using whole sections revealed a moderate agreement for membranous assessment (Cohen's kappa = 0.47) and a lower agreement for cytoplasm assessment (Cohen's kappa = 0.37). In an exploratory analysis, high cytoplasmic CD276 expression was associated with worse prognosis (OS, log-rank P = .043), but was not significant when adjusting for other clinical variables.

Conclusion: Although no prognostic value of CD276 expression was found, its high membranous expression (86%) in the PM samples of the study supports further research of its potential as a therapeutic target for this disease.

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