Resistance to PD-1 blockade (nivolumab) therapy in patients with advanced melanoma and renal cell carcinoma correlated with elevated oxidative tryptophan metabolism mediated by indoleamine 2,3 dioxygenase (IDO) following PD-1 blockade, suggesting that adaptive therapy resistance may be a barrier to inciting effective and durable clinical responses to immunotherapy.6 Poor patient survival after radiotherapy/chemotherapy (RT/CT) also correlated with elevated levels of systemic IDO activity,7 8 implicating IDO as a potential barrier to durable antitumor responses after RT/CT. This evidence concerns the gene IDO1 and hereditary clear cell renal cell carcinoma.