Immune-checkpoint blockade and candidate predictive biomarkers in HIV-negative Kaposi sarcoma: current evidence and a practical research framework

Kaposi sarcoma (KS) is a KSHV/HHV-8-driven vascular neoplasm with heterogeneous HIV-negative epidemiological settings. Immune-checkpoint blockade is biologically plausible, but direct clinical evidence remains limited to a small, non-comparative phase II cohort of pembrolizumab in classic or endemic KS. Its 71% best objective response rate is a signal that warrants confirmation, not comparative evidence or a basis for biomarker-guided treatment. This narrative review distinguishes established clinical observations from candidate translational hypotheses, appraises analytical and biological limitations of proposed markers, and outlines requirements for prospective subtype-stratified validation. PD-L1 expression, tumor mutational burden, and KSHV DNA should not be used as stand-alone selection or exclusion tests in routine care.