The Immunobiology of Kidney Cancer

Although kidney cancer (renal cell carcinoma [RCC]) is susceptible to immunotherapy, the immunologic aspects of the tumor microenvironment (TME) in RCC are relatively unique among tumor types. In RCC, baseline CD8 T-cell infiltration is associated with a worse prognosis. In addition, kidney cancer responds to programmed death-1/programmed death-ligand 1 blockade, despite a relatively low tumor mutation burden. Recent clinical data highlight the efficacy of combined immune checkpoint blockade and demonstrate that combining antiangiogenic agents with programmed death-1/programmed death-ligand 1 blockade has additive activity. Yet an important unanswered question in RCC is the nature of the antigens that are targeted by the immune system when immunotherapy is successful. Ongoing clinical studies are interrogating the multiple suppressive mechanisms in the RCC TME, including metabolic pathways such as those mediated by adenosine and tryptophan as well as cytokine-based therapies. Future regimens are likely to be combinatorial and may eventually be based on a broader understanding of the RCC TME and how it is modulated by both conventional and immune-based therapy.