CD248 as a bridge between angiogenesis and immunosuppression: a promising prognostic and therapeutic target for renal cell carcinoma

Renal cell carcinoma (RCC) is characterized by significant vascularization and immunogenicity, which contributes to drug resistance and immune escape. CD248, a pericytes marker in tumor vasculature, might help explain tumor microenvironment (TME) remodeling and serve as a novel therapeutic target.

CD248 appears to contribute to angiogenesis and immunosuppressive TME, and may thus be a promising prognostic and therapeutic target for RCC. CD248-based medication guidance might benefit RCC patients.

Transcriptome data and clinical information of RCC patients were obtained from The Cancer Genome Atlas (TCGA) database. ESTIMATE and microenvironment cell population (MCP)-counter algorithms were adopted to calculate immune and stromal contents. The prognostic value of TME was evaluated via Kaplan-Meier and Wilcoxon signed rank test. Pearson's correlation coefficient was employed to explore the correlation between angiogenesis and TME, and the relationship between CD248 and TME or RCC progression. CD248 overexpression and vascular colocalization in RCC were confirmed via histology staining. The weighted gene coexpression network analysis (WGCNA) and enrichment analysis were performed to explore CD248-mediated regulatory mechanism in angiogenesis and TME remodeling. CD248-based drug response was predicted through CellMiner database.

Tumor angiogenesis contributed to deteriorated RCC progression, which might be involved with immunosuppression. More specifically, upregulated immune checkpoints exhausted infiltrated T cells. CD248 overexpressed in RCC vessels correlated with TME and predicted a bad survival outcome. CD248 and coexpressed genes participated in angiogenesis and TME remodeling. Several clinical approved drugs that might inhibit CD248-mediated tumor promoting effects were selected. Conclusions: CD248 appears to contribute to angiogenesis and immunosuppressive TME, and may thus be a promising prognostic and therapeutic target for RCC. CD248-based medication guidance might benefit RCC patients.