Abstract
Retinoblastoma (RB) is the most common paediatric intraocular tumour. Currently, chemotherapy is widely used to reduce the chance of metastasis as well as for vision salvage. The limitations of chemotherapy for RB include chemoresistance and cytotoxicity. Recently, immunotherapy is considered for treating chemoresistant cancers. Although, several molecular targets are available for immunotherapy in different cancers, we were interested in B7H3, as it was differentially expressed between retinoblastoma and retina in our earlier proteomics study. Hence, in this study we validated the previous finding by Western blotting and immunohistochemistry on primary RB tumor samples. The results suggest significantly increased expression of B7H3 in RB tumor samples compared to retina by western blotting. Immunohistochemistry revealed spatial, inter and intratumoral heterogeneity in the primary RB tumor sections. Correlation of the B7H3 expression with clinical and histopathological data revealed significantly increased expression of B7H3 in poorly differentiated, non-neural invasive tumors and lower expression in neural invasion and severe anaplastic areas of the tumors. B7H3 expression did not significantly vary between low-risk and high-risk tumors. The study also revealed considerably reduced infiltration of T lymphocytes in RB. We conclude that B7H3 is prominently expressed in primary RB tumors and could be used for targeted therapy.
Highlights
Retinoblastoma (RB) is the most common paediatric intraocular tumour
We had earlier performed a membrane proteomics comparing primary retinoblastoma and retinal tissue[7]. While comparing their expression for immunotherapy molecules we found B7-H3 (CD276); one of the B7 family checkpoint molecule to be overexpressed in RB tumor compared to the retinal tissue
While the former could be addressed by a targeted approach to chemotherapy, the latter may require newer interventions like immunotherapy
Summary
Retinoblastoma (RB) is the most common paediatric intraocular tumour. Currently, chemotherapy is widely used to reduce the chance of metastasis as well as for vision salvage. Several monoclonal antibody based cancer immunotherapy molecules have been approved recently by Food and Drug Administration (FDA) This includes Programmed death-ligand 1 (PDL1), Programmed cell death protein 1 (PD1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), CD20 and CD54 for different cancers. Of these, both PDL1 and PD1 belong to the B7 family checkpoint molecule and their expression has been recently evaluated in RB tumour[4,5]. We had earlier performed a membrane proteomics comparing primary retinoblastoma and retinal tissue[7] While comparing their expression for immunotherapy molecules we found B7-H3 (CD276); one of the B7 family checkpoint molecule to be overexpressed in RB tumor compared to the retinal tissue. Since B7H3 is known to play a role as co-activator or co-inhibitor of T lymphocytes, we evaluated the distribution T lymphocytes using the markers CD3; CD4 and CD8 in the context of B7H3 expression in primary RB tumors
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