Journal
IMMUNITY
Volume 44, Issue 3, Pages 698-711Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2016.02.025
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Funding
- National Cancer Institute of France (INCa)
- Canceropole Ile de France
- MedImmune
- INSERM
- Austrian Federal Ministry of Science and Research (GEN-AU project Bioinformatics Integration Network)
- Qatar National Research Fund under its National Priorities Research Program [NPRP09-1174-3-291]
- European Commission (7FP, Geninca Consortium) [202230]
- Transcan ERAnet European project
- Association pour la Recherche contre le Cancer (ARC)
- Advanced Bioinformatics Platform for Personalised Cancer Immunotherapy (APERIM)
- Horizon 2020 [PHC-32, 633592]
- Haute-Normandie Region
- La Ligue Contre le Cancer de Haute-Normandie
- Cancer Research For Personalized Medicine (CARPEM)
- Paris Alliance of Cancer Research Institutes (PACRI)
- LabEx Immuno-oncology
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Microsatellite instability in colorectal cancer predicts favorable outcomes. However, the mechanistic relationship between microsatellite instability, tumor-infiltrating immune cells, Immunoscore, and their impact on patient survival remains to be elucidated. We found significant differences in mutational patterns, chromosomal instability, and gene expression that correlated with patient microsatellite instability status. A prominent immune gene expression was observed in microsatellite-instable (MSI) tumors, as well as in a subgroup of microsatellite-stable (MSS) tumors. MSI tumors had increased frameshift mutations, showed genetic evidence of immunoediting, had higher densities of Th1, effector-memory T cells, in situ proliferating T cells, and inhibitory PD1-PDL1 cells, had high Immunoscores, and were infiltrated with mutation-specific cytotoxic T cells. Multivariate analysis revealed that Immunoscore was superior to microsatellite instability in predicting patients' disease-specific recurrence and survival. These findings indicate that assessment of the immune status via Immunoscore provides a potent indicator of tumor recurrence beyond microsatellite-instability staging that could be an important guide for immunotherapy strategies.
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