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 Pessot, Jacques 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, 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 Pessot, Jacques 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
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.
Copyright © 2016 Elsevier Inc. All rights reserved.
Source: PubMed