# Integrative analyses of colorectal cancer show Immunoscore is a stronger predictor of patient survival than microsatellite instability

Source: https://onco.cc/key-papers/paper-mlecnik-immunoscore-msi-colorectal-immunity-2016/  
OnCo record `paper-mlecnik-immunoscore-msi-colorectal-immunity-2016` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Mismatch repair deficient bowel cancers do better partly because they are full of immune cells. When the immune cells are counted directly, the count predicts outcome better than the repair status does.

## Summary

Significant differences in mutational patterns, chromosomal instability and gene expression were found that correlated with microsatellite instability status. A prominent immune gene expression programme was observed in microsatellite-unstable tumours and in a subgroup of microsatellite-stable tumours. Unstable tumours had increased frameshift mutations, genetic evidence of immunoediting, higher densities of T-helper-1, effector-memory and in situ proliferating T cells and of inhibitory PD-1 and PD-L1 cells, high Immunoscores, and infiltration with mutation-specific cytotoxic T cells. In multivariate analysis, Immunoscore was superior to microsatellite instability in predicting disease-specific recurrence and survival.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Immunity
- Year: 2016
- DOI: 10.1016/j.immuni.2016.02.025
- Authors: Mlecnik B, Bindea G, Angell HK, et al.
- Findings: A prominent immune expression programme in unstable tumours and in a subgroup of stable tumours.; Genetic evidence of immunoediting in unstable tumours, with mutation-specific cytotoxic T cells.; Immunoscore outperformed microsatellite instability for disease-specific recurrence and survival.
- What it means: It explains the good prognosis of mismatch repair deficient disease as an immune effect rather than a repair effect, and identifies the microsatellite-stable tumours with an immune programme as the group worth trying immunotherapy in.
- Caveats: Retrospective cohorts.; Immunoscore requires standardised digital pathology and is not universally available.; Prognostic, not predictive of response to a checkpoint inhibitor.

## Sources

- Mlecnik et al., Immunity 2016: Immunoscore is a stronger predictor of survival than microsatellite instability: https://doi.org/10.1016/j.immuni.2016.02.025
- PubMed: https://pubmed.ncbi.nlm.nih.gov/26982367/

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- technologies: [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/)
- targets: [Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)](https://onco.cc/targets/mmr/), [PD-1](https://onco.cc/targets/pd1/)
- institutions: [Institut Curie](https://onco.cc/institutions/institut-curie/)
- pathways: [Antigen presentation & immune editing](https://onco.cc/pathways/antigen-presentation-immunoediting/), [The cancer-immunity cycle](https://onco.cc/pathways/cancer-immunity-cycle/), [Tumour microenvironment (TME)](https://onco.cc/pathways/tumor-microenvironment/)
- terms: [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/), [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/), [Neoantigen](https://onco.cc/terms/neoantigen/)
- journals: [Cell](https://onco.cc/journals/cell/)

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