Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability

Bernhard Mlecnik, Gabriela Bindea, Helen K. Angell, Pauline Maby, Mihaela Angelova, David Tougeron, Sarah E. Church, Lucie Lafontaine, Maria Fischer, Tessa Fredriksen, Maristella Sasso, Amélie M. Bilocq, Amos Kirilovsky, Anna C. Obenauf, Mohamad Hamieh, Anne Berger, Patrick Bruneval, Jean Jacques Tuech, Jean Christophe Sabourin, Florence Le PessotJacques Mauillon, Arash Rafii, Pierre Laurent-Puig, Michael R. Speicher, Zlatko Trajanoski, Pierre Michel, Richard Sesboüe, Thierry Frebourg, Franck Pagès, Viia Valge-Archer, Jean Baptiste Latouche, Jérôme Galon

Research output: Contribution to journalArticle

345 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)698-711
Number of pages14
JournalImmunity
Volume44
Issue number3
DOIs
Publication statusPublished - 15 Mar 2016

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Mlecnik, B., Bindea, G., Angell, H. K., Maby, P., Angelova, M., Tougeron, D., Church, S. E., Lafontaine, L., Fischer, M., Fredriksen, T., Sasso, M., Bilocq, A. M., Kirilovsky, A., Obenauf, A. C., Hamieh, M., Berger, A., Bruneval, P., Tuech, J. J., Sabourin, J. C., ... Galon, J. (2016). Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability. Immunity, 44(3), 698-711. https://doi.org/10.1016/j.immuni.2016.02.025