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Lata Singh, Mithalesh Kumar Singh, Moshahid Alam Rizvi, Seema Kashyap; Interaction of Immune Checkpoints in Tumor-Stromal Microenvironment of Primary and Chemoreduced Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2319. doi: https://doi.org/.
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nteractions between malignant and non-malignant cells create the tumor microenvironment (TME). The non-malignant cells of the TME have a dynamic and tumor-promoting function at all stages of carcinogenesis. Cytotoxic T lymphocyte associated antigen 4 (CTLA4), programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are key components of immune checkpoint pathway. They play a role in the regulation of T-cell activation and their expression in TME constitutes a predictive biomarker in cancers. It has recently been shown that chemotherapeutic agents could modify tumor microenvironment. Therefore, we investigated the expression of PD-1, PD-L1 and CTLA-4 in primary and chemoreduced retinoblastoma to define their significance in tumor microenvironment with patient prognosis.
Expression of immune markers (PD-1, PD-L1 and CTLA-4 protein) was evaluated in 75 prospective cases of primary (Group I) and 25 cases of chemoreduced (Group II) retinoblastoma specimens by immunohistochemistry. mRNA expression of genes of interest were investigated by quantitative real time PCR (qPCR) and results were correlated with clinicopathological parameters and patient outcome by statistical analysis
Differential expression pattern of PD-1, PD-L1 and CTLA-4 proteins was found in both group I (primary retinoblastoma) and group II (chemoreduced retinoblastoma) cases. Immunohistochemistry showed cytoplasmic/membranous staining of these immune markers using their respective antibodies. Increased expression of PD-1, PD-L1 and CTLA-4 was found in stromal/immune cells of group II as compared to Group I. Expression of these immune markers showed significant correlation with poor tumor differentiation, tumor invasion and patient outcome (p<0.05).
This is the first of its kind study investigating the role of immune markers in primary retinoblastoma and their alteration in expression after chemotherapy. Tumor microenvironment of retinoblastoma showed expression of PD-L1 in primary patients and increased expression in PD-L1, CTLA-4 and PD-1 after chemotherapy. This paves the way for development of immunotherapy as a new strategy for treatment of chemoreduced retinoblastoma.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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