Immunoediting and precision biomarkers in prostate cancer: The emerging role of liquid biopsy, immune contexture and HLA genotype (Review)

Abstract

Prostate cancer (PCa) remains a leading cause of cancer-related mortality in men despite advances in screening and localized treatment. The clinical heterogeneity of PCa, ranging from indolent disease to aggressive, lethal phenotypes, underscores the urgent need for reliable biomarkers that improve diagnosis, prognostication and therapeutic decision-making. While prostate-specific antigen testing has reduced mortality, its limited specificity has resulted in overdiagnosis and overtreatment. The present review provides a comprehensive overview of contemporary and emerging biomarkers that support a precision-medicine approach to PCa management. The present review summarizes established and novel diagnostic, prognostic and predictive biomarkers, including serum- and urine-based assays, genomic and transcriptomic signatures and multiparametric imaging. Particular emphasis is placed on liquid biopsy technologies (circulating tumor cells, circulating tumor DNA and extracellular vesicles), which offer minimally invasive, real-time insights into tumor burden, molecular evolution and treatment resistance, although their clinical implementation remains context-dependent and is currently most established in advanced disease settings rather than routine early-stage management. The present review discusses the strengths and limitations of these platforms, highlighting disease-stage dependency, technical variability and sensitivity constraints. Beyond tumor-intrinsic markers, tissue-based immune biomarkers that capture the tumor immune microenvironment, including immune cell density, spatial organization, checkpoint expression and immune-related gene signatures, are explored. Evidence indicates that 'immune-hot' tumors characterized by CD8+ T-cell infiltration and interferon-γ signaling are associated with improved outcomes, whereas immunosuppressive macrophage- or regulatory T-cell-dominant profiles predict poor prognosis. However, these associations are not uniform across studies and PCa remains largely resistant to immunotherapy, underscoring the need to improve the understanding of immune evasion mechanisms and the contextual limitations of immune biomarkers. Furthermore, the present review examines the emerging role of germline human leukocyte antigen class I genotype as a prognostic and predictive biomarker, explicitly integrating it with tissue-based immune contexture and liquid biopsy readouts by proposing immunoediting as a unifying mechanistic framework that links allele-specific antigen presentation to immune infiltration. Finally, the present review highlights the prognostic significance of preexisting tumor-antigen-specific CD8+ T cells, which reflect an active antitumor immune response and predict a favorable progression-free survival and responsiveness to immunotherapeutic strategies. Collectively, the present review underscores the need for standardized, multimodal biomarker integration and prospective validation to enable personalized, immune-aware management of PCa.