Implementing Immunoscore in colorectal cancer: lessons from cohort studies, limitations and barriers to adoption

The Immunoscore (IS) quantifies the immune contexture of colorectal cancer (CRC) by measuring CD3⁺ and CD8⁺ T-cell densities in the tumour centre and invasive margin, providing superior prognostic performance compared with TNM staging and mismatch-repair (MMR) status alone. Large international cohort studies have validated its ability to predict benefit from adjuvant chemotherapy in stage III colon cancer. More recently, Immunoscore-IC - a refined version that incorporates PD-L1⁺ cell density and spatial interactions - has emerged as the first biomarker capable of identifying the subset of patients with proficient-MMR (pMMR/MSS) metastatic CRC who derive significant benefit from immune checkpoint inhibitors. Despite these advances, technical requirements, biological limitations, and reliance on retrospective data continue to hinder widespread clinical adoption. Addressing some of these challenges could enhance its utility and facilitate broader integration into routine pathology practice. In this commentary, we place landmark IS publications within the evolving research landscape, including papers published in The Journal of Pathology Clinical Research; integrate findings from recent international validation cohorts and adjuvant trials; and highlight the growing evidence supporting IS as a robust prognostic tool with clear predictive implications for both chemotherapy and immunotherapy in CRC.