Immunoscore and beyond: evolution and clinical integration of immune contexture-based biomarkers across solid tumours

Abstract

The tumour immune microenvironment is increasingly recognised as a critical determinant of cancer progression, prognosis, and therapeutic response, challenging the sufficiency of anatomy-based staging systems such as TNM. The Immunoscore (IS), originally validated in colorectal cancer, provides a standardised, spatially resolved assessment of CD3(+) and CD8(+) T cells within the tumour core (TC) and invasive margin (IM). Expanding upon this framework, adapted and modified IS models, as well as computational and imaging-based surrogates, have been investigated across multiple solid malignancies, including non-small-cell lung cancer, hepatocellular carcinoma, head and neck cancers, gastric cancer, melanoma, and bladder cancer. This review synthesises the current evidence, emphasising both the translational potential and methodological heterogeneity of IS-based approaches. High IS or adapted scores generally correlate with improved survival and may refine risk stratification, complementing conventional TNM staging. However, inter-study variability limits comparability and reproducibility. Retrospective designs, single-centre cohorts, limited external validation, and potential overfitting in computational models further constrain the strength of evidence. Biological context dependency, immune-exclusion phenotypes, and the dynamic evolution of the tumour immune landscape complicate interpretation, underscoring that high immune cell density does not universally equate to effective antitumour immunity. Overall, the IS and related immune-contexture classifiers constitute a biologically grounded framework that bridges tumour immunology and clinical oncology. While promising, widespread clinical implementation requires methodological harmonisation, prospective validation, and integration with genomic, systemic, and imaging biomarkers. By highlighting both achievements and current limitations, this review provides a balanced perspective on the potential and challenges of translating immune contexture-based metrics into precision oncology.