Single-cell transcriptomic analyses provide insights into the tumor microenvironment heterogeneity and invasion phenotype in retinoblastoma.
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BACKGROUND: As the most common intraocular malignant tumor, retinoblastoma (RB) is associated with high mortality during early childhood. The heterogeneous cellular composition of the tumor microenvironment (TME) plays a pivotal role in modulating immune responses, tumor growth and metastasis progression. However, the landscape of TME heterogeneity and cell-cell communication networks in RB remain poorly characterized. METHODS: Different phenotypes of RB were characterized by integrated single-cell sequencing data. Cellular subclusters of three principal TME components were systematically identified. CellChat analyzed package was employed to depict intercellular communications across all types of cells in TME. Next, pseudotime trajectory analyses were performed with Monocle package. CIBERSORT algorithms (LM22 signature matrix) and CIBERSORTx platform were employed to characterize immune cell infiltration landscape from microarray data. Finally, functional enrichment profiling elucidated associations between TME subcluster signatures and extraocular invasion phenotypes of RB. RESULTS: Characteristic subclusters of TME components, such as MG1 in tumor-associated macrophages (TAMs) and AC1 in astrocyte-like cells were probably associated with RB extraocular invasion in different ways. And RB invasive progression might be relevant with the cell-cell communications landscape change between TME-related cell populations. Trajectory analysis revealed the potential correlation of RB invasion with the increase of immature TAMs and the decrease of terminally differentiated astrocyte-like cells. Functional enrichment analysis further profiled the distinct molecular feature of characteristic subclusters. CONCLUSIONS: This study systematically delineates TME heterogeneity landscapes across non-invasive versus invasive RB, providing mechanistic insights into intercellular communications within TME. Our findings might have the potential to develop microenvironment-targeted therapeutic strategies in RB management.