Abstract
Retinoblastoma is a common pediatric intraocular cancer, originating from cone precursors. The development of immunotherapies can help eradicate the tumor without vision loss, which would largely improve the quality of life of patients with retinoblastoma. Investigation of the tumor immune microenvironment provides knowledge for developing novel immunotherapies in cancer. However, the immune cell infiltrative landscape of retinoblastoma is unknown. Here, we compared the relative expression of immune gene signatures among 59 patients with retinoblastoma. The patients were divided into two subgroups according to the 28 types of immune cell infiltration (ICI) scores. We found that a subgroup with high ICI scores had increased expression levels of late cone markers, while the other subgroup exhibited larger tumor size and metastasis propensity. Furthermore, hypermethylated genes in the high-ICI subgroup were associated with immune regulation in the tumor microenvironment, suggesting that DNA methylation may play a vital regulatory role in retinoblastoma immunity. Our study provides a comprehensive framework for the systemic analysis of the influences of epigenetic events on the tumor immune microenvironment. We anticipate that our assay can not only provide insights into tumor immune regulation but also open up the perspectives for the identification of novel immunotherapy targets for retinoblastoma.
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