B7-H3 and GD2 overexpression as immunotherapeutic targets in retinoblastoma

Abstract

Retinoblastoma (RB) is the most prevalent malignant eye tumor in children. Chimeric antigen receptor T-cell therapy showed significant promise in treating blood cancers and could potentially be effective for RB. A critical step toward advancing this therapy involves identifying surface antigens on RB cells. This study focuses on evaluating the expression of tumor antigens and immune checkpoint proteins in primary and secondary enucleated RB samples and analyzing their relationship with clinical and pathological data. We performed immunohistochemical analysis on 94 formalin-fixed, paraffin-embedded RB tissue samples from Thai patients to assess the expression of B7-H3, GD2, CD171, and PD-L1. B7-H3 was the most frequently expressed antigen, appearing in 51.06% of samples (48/94) with mild to moderate membranous intensity. GD2 was present in 36.17% of samples (34/94) with moderate staining intensity. CD171 was detected in 9.57% of samples (9/94), showing weak to mild membranous intensity. PD-L1 was the least expressed, found in only 4.26% of samples (4/94) with mild to moderate membrane staining. There were no significant correlations between the expression of these antigens and patient characteristics. Our study emphasizes the variability in tumor antigen expression in RB. The notable expression of B7-H3 and GD2 suggests they could be promising targets for immunotherapy. These findings encourage further investigation into multi-specific or combination immunotherapies for treating retinoblastoma.