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The Immunoscore is a standardised measure of the T-lymphocyte infiltration of a tumour — densities of CD3+ and CD8+ cells at the tumour centre and invasive margin, quantified by immunohistochemistry and digital pathology. It converts the “immune contexture” into a reproducible score, with prognostic and predictive value, complementary to the classical TNM histopathological classification.

Principle and workflow

From tumour sections, the CD3 and CD8 markers are revealed by immunohistochemistry; the slides are digitised, then cell densities are quantified automatically in two key regions — the tumour centre and the invasive margin. These densities are converted into a categorical score, from lowest to highest. What distinguishes the Immunoscore from a simple count of infiltrating lymphocytes is precisely its standardisation: antibodies, thresholds, algorithms and quality control are defined so that the result is reproducible and comparable from one centre to another.

Variants and options

Beyond the CD3/CD8 pair, extended scores incorporate other populations (B lymphocytes, memory cells) or combine the Immunoscore with patho-molecular parameters such as microsatellite instability (MSI) status or mutational burden. The index has been evaluated in several tumour sites and has been the subject of dedicated inter-observer and inter-centre reproducibility studies, an indispensable step for clinical use.

When and why this technique

The Immunoscore provides prognostic information largely independent of TNM and helps to anticipate the benefit of adjuvant chemotherapy — useful, for example, to stratify patients with stage III colon cancer.

A few reservations bound its scope. It is a tissue biomarker: it requires a resected tumour of good quality and a controlled pre-analytical chain. Its robustness rests entirely on strict standardisation (staining, digitisation, image analysis): optical assessment on an ordinary slide is too discordant, and digital pathology is indispensable to a reproducible measurement. It measures a precise dimension — the cytotoxic T infiltrate (CD3/CD8) — and is conceived as a complement, not a substitute, to TNM classification and established markers; its value was first established in specific sites, colon cancer foremost.

Inovarion’s expertise

Inovarion’s scientists have long contributed to validating the Immunoscore in international multicentre studies. This work established the clinical performance of the consensus Immunoscore in predicting survival and the response to chemotherapy in stage III colon cancer (SITC study, 763 patients split into two cohorts), and confirmed its value in the Asian population. This translational expertise links the bench to clinical decision-making: staining standardisation, automated quantification by digital pathology, inter-centre robustness and association with patho-molecular parameters (MSI). Inovarion supports the design, execution and validation of immune signatures on cohorts, from tissue to statistical analysis.

See also: Immunohistochemistry & multiplex immunofluorescence (underlying technique).

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Key publications

  • Mlecnik et al. Multicenter International Society for Immunotherapy of Cancer Study of the Consensus Immunoscore for the Prediction of Survival and Response to Chemotherapy in Stage III Colon Cancer. Journal of Clinical Oncology, 2020. Record → · PubMed
  • Mlecnik et al. Clinical Performance of the Consensus Immunoscore in Colon Cancer in the Asian Population from the Multicenter International SITC Study. Cancers (Basel), 2022. Record → · PubMed