Prevalence and Clinical Association of CD276 (B7-H3) Expression in Pleural Mesothelioma: Results From the European Thoracic Platform Mesoscape Project
Authors: Haberecker Martina , Rüschoff Jan H. , Andriakopoulou Charitini , Gray Steven G. , Nackaerts Kristiaan , De Perrot Marc , Brcic Luka , Nadal Ernest , Tsimpoukis Sotirios , Ampollini Luca , Aerts Joachim G. , Kirschner Michaela B. , Monkhorst Kim , Weynand Birgit , Bavaghar-Zaeimi Fatemeh , Samarzija Miroslav , Llatjos Roger , Finn Stephen P. , Silini Enrico , Von Der Thüsen Jan , Vagenknecht Patrick , Tsourti Zoi , Kerr Keith M. , Kammler Roswitha , Peters Solange , Baas Paul , Opitz Isabelle , Stahel Rolf A. , Curioni-Fontecedro Alessandra ,   for the ETOP Mesoscape Consortium, Stahel Rolf , Hiltbrunner Anita , Kammler Rosita , Vagenknecht Patrick , Christoffel Miriam , Ruepp Barbara , Dafni Urania , Tsourti Zoi , Zygoura Panagiota , Vervita Katerina , Dimopoulou Georgia , Andriakopoulou Charitini , Stavrou Androniki , Rüschoff Jan H. , Haberecker Martina , Dettwiler Susanne , Prutek Fabiola , Mittmann Christiane , Opitz Isabelle , Baas Paul , Opitz Isabelle , Vrugt Bart , Friess Martina , Matter Alessandra , Spichiger-Häusermann Chloé , Kirschner Michaela B. , Baas Paul , Monkhorst Kim , Nackaerts Kristiaan , Verbeken Eric , Weynand Birgit , Peeters Liesbet , Ampollini Luca , Tiseo Marcello , Silini Enrico Maria , Gnetti Letizia , de Perrot Marc , Zaeimi Fatemeh B. , Brcic Luka , Samarzija Miroslav , Seiwerth Sven , Jakopovic Marko , Nadal Ernest , Cardenal Felipe , Llatjos Roger , Lorente Susana , Syrigos Konstantinos , Vamvakaris Ioannis , Tsimpoukis Sotirios , Boura Paraskevi , Gray Steven , Finn Stephen P. , Nur Mutaz Mohammed , Baird Anne-Marie , Barr Martin , Cuffe Sinead , Gately Kathy , Aerts Joachim , Thüsen Jan von der 
Published: February 2025

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.