Tumour-agnostic immunotherapy: aligning biological rationale, biomarker precision, and real-world implementation

Abstract

Summary Tumour-agnostic immunotherapy has reshaped precision oncology by showing that treatment benefit can, in selected settings, be predicted by a shared biological state rather than anatomical origin. Microsatellite instability-high or mismatch repair-deficient cancer is the clearest example, with durable responses across diverse malignancies. By contrast, broader biomarkers show that pan-cancer applicability cannot be inferred from a measurable molecular feature alone. Tumour lineage, antigen presentation, immune microenvironment, prior therapy, and health-system context all influence whether a tumour-agnostic indication translates into real-world benefit. We examine the biological principles that distinguish robust from context-dependent immunotherapy biomarkers, the uncertainty created by rare cancers and incomplete evidence, and the implementation challenges that arise when therapeutic access outpaces biomarker infrastructure. Using Australia's broad reimbursement of immune checkpoint inhibitors for immunotherapy-sensitive advanced cancers as a case study, we consider implications for emerging pan-tumour platforms. We argue for biologically informed access embedded within learning health systems.