Comprehensive Analysis of the Immune Cell Infiltration Landscape and Immune-Related Methylation in Retinoblastoma

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.

Transcriptome analysis reveals molecularly distinct subtypes in retinoblastoma

“…In contrast, subtype 2 seems to be the immune desert as compared with subtype 1, suggesting the immune cell therapy might not be effective in these subpopulations 31 . Mao et al also identified two mutually exclusive immune cell infiltration patterns in two major molecular subtypes 32 , highlighting that different immune cell-based strategy would be considered in the management of retinoblastoma.…”

Pediatric Solid Cancers: Dissecting the Tumor Microenvironment to Improve the Results of Clinical Immunotherapy

“…Mao et al identified two immunological subgroups of retinoblastoma based on the immune profiles of 28 types of immune cells. These subgroups of patients had different clinical characteristics and gene expression profiles [ 126 ]. By studying the distinct DNA methylation patterns between the two subgroups, Mao et al found that immune cell infiltration was related to retinoblastoma migration and metastatic progression [ 126 ].…”

“…These subgroups of patients had different clinical characteristics and gene expression profiles [ 126 ]. By studying the distinct DNA methylation patterns between the two subgroups, Mao et al found that immune cell infiltration was related to retinoblastoma migration and metastatic progression [ 126 ]. An integrative single-cell transcriptome and whole-exome sequencing analysis of retinoblastoma patients revealed that the TME in retinoblastoma was composed of tumor-associated macrophages (TAMs), astrocyte-like cells, and cancer-associated fibroblasts [ 127 ].…”

Oncogenic Proteomics Approaches for Translational Research and HIV-Associated Malignancy Mechanisms

“…Recent studies relating to proteomics and Immune Cell Infiltration (ICI) have demonstrated two types of gene subgroups responsible for tumor metastasis. Furthermore, hypermethylation has been identified as a potential mechanism for treating Rb, as it regulates the TIMT in the high-ICI groups [ 103 ]. Biopsies have long been considered unsafe practices with a high-risk of ocular spread in Rb, insisting that safer approaches are needed for therapeutic management [ 104 ].…”