Landscape of immune cell infiltration in clear cell renal cell carcinoma to aid immunotherapy

Abstract

The tumor microenvironment, comprised of tumor cells and tumor-infiltrating immune cells, is closely associated with the clinical outcome of clear cell renal cell carcinoma (ccRCC) patients. However, the landscape of immune infiltration in ccRCC has not been fully elucidated. Herein, we applied multiple computational methods and various datasets to reveal the immune infiltrative landscape of ccRCC patients. The tumor immune infiltration (TII) levels of 525 ccRCC patients using a single-sample gene were examined and further categorized into immune infiltration subgroups. The TII score was characterized by distinct clinical traits and showed a significant divergence based on gender, grade, and stage. A high TII score was associated with the ERBB signaling pathway, the TGF-β signaling pathway, and the MTOR signaling pathway, as well as a better prognosis. Furthermore, patients with high TII scores exhibited greater sensitivity to pazopanib. The low TII score was characterized by a high immune infiltration level of CD8⁺ T cells, T follicular helper cells, and regulatory T cells (Tregs). Moreover, the immune check point genes, including CTLA-4, LAG3, PD-1, and IDO1, presented a high expression level in the low TII score group. Patients in the high TII score group demonstrated significant therapeutic advantages and clinical benefits. The findings in this study have the potential to assist in the strategic design of immunotherapeutic treatments for ccRCC.