Application of Immune Checkpoint Inhibitors in the Treatment of Renal Cell Carcinoma: Current Status, Challenges, and Future Directions

In recent years, immune checkpoint inhibitors (ICI) have revolutionized the treatment landscape of renal cell carcinoma (RCC), significantly enhanced patient outcomes and expanded therapeutic options beyond traditional surgical and targeted approaches. In this review, we provide a comprehensive review of the current applications of ICI in RCC therapy, elucidating their mechanisms of action, clinical efficacy across both clear cell and non-clear cell subtypes, and safety profiles. We compare the effectiveness of monotherapy versus combination therapies, demonstrating how synergistic approaches can improve efficacy and durability of responses. Furthermore, we explore the integration of multi-omics technologies, such as single-cell RNA sequencing and spatial transcriptomics, which are pivotal in predicting ICI response and addressing resistance mechanisms. Our discussion also addresses the critical challenges in RCC immunotherapy, including primary and acquired resistance, economic and ethical barriers, and the management of immune-related adverse events. By synthesizing current research and clinical findings, this review aims to provide valuable insights for optimizing RCC immunotherapy, fostering the development of more effective and individualized treatment protocols, and ultimately improving patient survival and quality of life.