While this study was in preparation, another publication described a new mouse ccRCC model based on CRISPR-Cas9 mediated combinatorial mutation of Vhl, Pbrm1, Keap1 and Tsc1 that is also similarly resistant to single, double and triple anti-PD-1, anti-CTLA-4 and HIF-2α inhibition therapies36. Here, VHL is linked to nonpapillary renal cell carcinoma.