Multicenter retrospective analysis of association of 5α-reductase inhibitor prescription with ICI efficacy in metastatic renal cell carcinoma

Reliable predictive biomarkers for efficacy of immune checkpoint inhibitors (ICIs) in metastatic renal cell carcinoma (mRCC) are lacking. Recent studies suggested that androgen receptor (AR) signaling plays a role in regulating CD8+ T-cell function, implying that 5α-reductase inhibitors (5-ARIs), which lower androgen activity, could enhance antitumor immunity. A multicenter retrospective study in China evaluated the impact of 5-ARI use on efficacy of ICIs for mCC. Of 185 patients receiving ICIs for mRCC, 78 had a history of using 5-ARIs for at least 12 months before starting ICIs. The 5-ARI group had better response to ICIs (objective response rate 59.8% versus 39.8%; p=0.0075) as well as better progression-free survival and overall survival. Single-cell RNA sequencing analysis revealed that 5-ARI treated patients exhibited a reduced presence of regulatory T cells and CD8 T-cell exhaustion, and lower PD-1 expression in these cells, suggesting an immunologically favorable modification of the tumor. The authors conclude that a history of 5-ARI use was associated with improved efficacy of ICIs for mRCC.