PD-1 (IM) expression was associated with better PFS whereas AXL expression by tumor cells (TC) was associated with worse PFS (table). LAG-3 expression tend to be associated with worse OS. PBRM-1 loss (15%) was associated with better OS and PFS and with a higher density of CD8 T-cells (p = 0.001) and CD163-macrophages (p = 0.01) (CT) and a higher expression of LAG-3 (CT) (p = 0.01) and PD-1 (CT) (p = 0.02). BAP-1 loss was not associated with PFS (p = 0.6) nor OS (p = 0.9) in this cohort.

To validate the findings, we analyzed an independent cohort of 63 patients with metastatic ccRCC treated with therapies blocking PD-1 (e.g., nivolumab) or its ligand PD-L1 (e.g., atezolizumab)...Patients whose tumors showed biallelic PBRM1 loss had significantly prolonged OS and PFS compared to patients without PBRM1 LOF (log-rank test P = 0.0074 and 0.029, respectively) (Fig. 2C and fig. S5), and they experienced sustained reductions in tumor burden (Fig. 2D).