Construction of an Immune Escape-Related Signature in Clear Cell Renal Cell Carcinoma and Identification of the Relationship between IFNAR1 and Immune Infiltration by Multiple Immunohistochemistry

SIMPLE SUMMARY: This research found that a higher immune escape score was significantly correlated with a shorter survival time. Meanwhile, through the validation of the external cohort and the correlation analysis of the immune microenvironment, we proved that IFNAR1 is the key gene regulating immune escape in ccRCC, and we also found that the function of IFNAR1 in promot-ing immune activation is achieved by facilitating the infiltration of CD4(+) T cells and CD8(+) T cells. Our research found a new key molecule that regulates the immune mi-croenvironment of ccRCC, which could accurately predict the efficacy of ccRCC im-munotherapy, thus providing a new idea for immunotherapy in ccRCC. ABSTRACT: Background: In the past decade, immunotherapy has been widely used in the treatment of various tumors, such as PD-1/PD-L1 inhibitors. Although clear cell renal cell carcinoma (ccRCC) has been shown to be sensitive to immunotherapy, it is effective only in several cases, which brings great obstacles to anti-tumor therapy for patients. Lawson et al. have successfully identified 182 “core cancer innate immune escape genes” whose deletion makes cancer cells more sensitive or resistant to T-cell attack. Methods: In this research, we sought to explore genes closely associated with ccRCC among the 182 core cancer innate immune escape genes. We used online databases to screen mutated genes in ccRCC, and then used ConsensusClusterPlus to cluster clinical samples to analyze differences in clinical prognosis and immune components between the two subgroups. In addition, the immune escape score was calculated using lasso cox regression, and a stable tumor immune escape-related nomogram was established to predict the overall survival of patients. Results: Higher immune escape score was significantly correlated with shorter survival time. Meanwhile, through the validation of the external cohort and the correlation analysis of the immune microenvironment, we proved that IFNAR1 is the key gene regulating immune escape in ccRCC, and we also found that the function of IFNAR1 in promoting immune activation is achieved by facilitating the infiltration of CD4(+) T cells and CD8(+) T cells. IFNAR1 regulates the malignant behavior of ccRCC by inhibiting the proliferation and migration properties. Conclusions: IFNAR1 may become a key biomarker for evaluating the efficacy of ccRCC immunotherapy and may also be a potential target for immunotherapy.