Renal cell carcinoma (RCC) is a biologically diverse malignancy with a rising global incidence and a high propensity for metastasis, particularly in its clear cell subtype. While traditional treatments have centered on surgery and targeted therapies, immunotherapy has emerged as a transformative approach in the management of advanced RCC. This review explores the evolution of immunotherapy in RCC, from early cytokine-based treatments to the advent of immune checkpoint inhibitors (ICIs) and their integration with tyrosine kinase inhibitors (TKIs). We detail the immunologic mechanisms underpinning these therapies, the rationale from preclinical models, and the pivotal clinical trials that redefined standard of care. Challenges such as immune resistance, tumor heterogeneity, and immune escape mechanisms are critically analyzed, highlighting tumor-intrinsic and microenvironmental factors. Lastly, we examine ongoing innovations including novel immune checkpoints, cytokine modulators, CAR-T therapies, and neoantigen-based vaccines, offering a forward-looking perspective on enhancing immunotherapeutic efficacy and personalization in RCC management.
Peshin et al. (2025) studied this question.