Immune checkpoint inhibitor-based therapy for advanced clear cell renal cell carcinoma: A narrative review

The prognosis for advanced clear cell renal cell carcinoma (ccRCC) is not satisfactory, even though its treatment has evolved rapidly over the past 20 years. Systemic ccRCC treatment options mainly involve antiangiogenic therapy, immune checkpoint blockade, or a combination of these therapies, and as more clinical evidence becomes available, immune checkpoint inhibitors (ICIs) are increasingly dominant. Conventional ICIs lead to the restoration of T-cell activation and a reduction in T-cell depletion by specifically blocking programmed cell death 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1) or cytotoxic T lymphocyte antigen 4 (CTLA-4), ultimately enhancing the antitumor immune response. There is no doubt that these therapies have achieved some clinical efficacy in the overall ccRCC population, but response rates and durability remain a great challenge. Therefore, novel immune checkpoints or new combination therapeutic strategies based on ICIs continue to be sought and developed. This review will provide a comprehensive overview of ICI-based therapeutic strategies in advanced ccRCC, including their mechanisms of action and the latest clinical evidence.