Clinical characterization and immunosuppressive regulation of IL15RA in Kidney renal papillary cell carcinoma through 324 samples

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Abstract Stimulation of renal cell carcinoma with exogenous IL-15Rα, encoded by IL15RA, could induce epithelial-mesenchymal transition (EMT) and promote cell migration and invasion. To assess the validity of IL15RA in predicting the prognosis of kidney renal papillary cell carcinoma (KIRP) and to explore its therapeutic potential for KIRP, we performed a retrospective RNA-seq data analysis of a cohort of 290 patients with KIRP from the TCGA database and 34 patients from the GEO database. We found that IL15RA is downregulated in KIRP samples compared to normal samples, but upregulated in KIRP samples with relatively higher malignancy and later stages. Univariate cox analysis and multivariate cox regression analysis suggested that upregulated IL15RA is an independent risk factor for poor prognosis of KIRP. Functional enrichment analysis showed that IL15RA in KIRP may play an essential role in inflammatory and immune response through rap1 signaling pathway. Immune cell infiltration analysis revealed that the infiltration level of M2 macrophages was positively correlated with IL15RA expression. Moreover, IL15RA showed a strong positive relationship with known inhibitory immune checkpoints, which may represent a novel mechanism of immune escape and provide new insights into the potential of immunotherapy for KIRP.

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