Immune-Related Proteomic Profiling in Clear Cell Renal Cell Carcinoma: Tissue and Soluble Biofluid Biomarkers

Clear cell renal cell carcinoma (ccRCC) shows complex interactions with the tumor microenvironment, involving a range of immune checkpoint proteins and circulating biomarkers that may influence disease progression and response to treatment. Recent technological advances have identified tissue-based and circulating immune-related proteomic targets such as programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and circulating interleukin-8 (cIL-8) as potential diagnostic, prognostic and predictive biomarkers. Despite significant progress, ccRCC remains a major clinical challenge due to its diverse molecular and immunological characteristics that hinder the clinical utility of these biomarkers. The present review provides an updated overview of the current evidence regarding immune-related proteomic biomarkers in ccRCC, including both tissue-derived and circulating proteins. Herein, we discuss the potential diagnostic, prognostic, and predictive value of such agents, emphasizing their biological significance and potential to guide personalized immunotherapeutic strategies. Particular attention is given to the developing liquid-biopsy-based techniques and their application as novel minimally invasive methods of identifying new targets for disease monitoring and treatment evaluation. Finally, we focus on emerging therapeutic approaches and combined strategies, highlighting how biomarker-driven precision oncology continues to reshape ccRCC management.