BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC), but response rates remain heterogeneous, and reliable predictive biomarkers are lacking. Recent studies suggest that androgen receptor (AR) signaling plays a role in regulating CD8 METHODS: We conducted a multicenter retrospective cohort study of 185 patients with mRCC who received ICIs. Patients were stratified based on their history of 5-ARI use. Baseline characteristics included age, body mass index, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group, programmed death-ligand 1 (PD-L1) expression levels, tumor stage, and metastasis sites. The primary endpoints were progression-free survival (PFS) and overall survival (OS), analyzed using Cox proportional hazards models. Secondary endpoints included objective response rate (ORR) and disease control rate (DCR). Key immunological insights were gained through single-cell RNA sequencing analysis of tumor samples. RESULTS: Patients with a history of 5-ARI use demonstrated improved ORR (59.8% vs 39.8%, p=0.0075) and DCR (87.0% vs 78.7%, p=0.1747) compared with those without. The median PFS and OS were significantly longer in the 5-ARI group, with HRs of 0.64 (95% CI: 0.47 to 0.86, p=0.0085) for PFS and 0.65 (95% CI: 0.47 to 0.90, p=0.0271) for OS. Subgroup analysis further indicated enhanced ICI efficacy with 5-ARI use across age, IMDC risk scores, and PD-L1 expression levels. Single-cell RNA sequencing analysis revealed that 5-ARI treated patients exhibited a reduced presence of regulatory T cells and CD8 T-cell exhaustion (CD8 Tex), and lower programmed cell death protein-1 expression in CD8 Tex cells, suggesting an immunologically favorable modification of the tumor. CONCLUSION: A history of 5-ARI use is associated with improved responses to ICI therapy in mRCC, potentially through AR-related modulation of CD8