Antigenic targets in clear cell renal cell carcinoma

Immune checkpoint inhibitors (ICIs) have transformed the management of advanced renal cell carcinoma (RCC), but most patients still do not receive a long-term benefit from these therapies, and many experience off-target, immune-related adverse effects. RCC is also different from many other ICI-responsive tumors, as it has only a modest mutation burden, and total neoantigen load does not correlate with ICI response. In order to improve the efficacy and safety of immunotherapies for RCC, it is therefore critical to identify the antigens that are targeted in effective anti-tumor immunity. In this review, we describe the potential classes of target antigens, and provide examples of previous and ongoing efforts to investigate and target antigens in RCC, with a focus on clear cell histology. Ultimately, we believe that a concerted antigen discovery effort in RCC will enable an improved understanding of response and resistance to current therapies, and lay a foundation for the future development of “precision” antigen-directed immunotherapies.