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

Bernhard Mlecnik 1, 2 Gabriela Bindea 3 Helen Angell 4 Pauline Maby 2 Mihaela Angelova 2, 5 David Tougeron 6 Sarah Church 2 Lucie Lafontaine 4 Maria Fischer 5 Tessa Fredriksen 7, 2 Maristella Sasso 2 Amélie Bilocq 2 Amos Kirilovsky 8 Anna Obenauf 9 Mohamad Hamieh 10 Anne Berger 11 Patrick Bruneval 12 Jean-Jacques Tuech 13 Jean-Christophe Sabourin 14 Florence Le Pessot 15 Jacques Mauillon 16 Arash Rafii 17 Pierre Laurent-Puig 11 Michael Speicher 9 Zlatko Trajanoski 18 Pierre Michel 19 Richard Sesboüé 20 Thierry Frebourg 20 Franck Pagès 4 Viia Valge-Archer 21 Jean-Baptiste Latouche 22, 23 Jérôme Galon 3
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.
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https://hal-normandie-univ.archives-ouvertes.fr/hal-02379906
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Submitted on : Monday, November 25, 2019 - 10:48:35 PM
Last modification on : Friday, September 18, 2020 - 2:34:59 PM

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Bernhard Mlecnik, Gabriela Bindea, Helen Angell, Pauline Maby, Mihaela Angelova, et al.. Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability. Immunity, Elsevier, 2016, 44 (3), pp.698-711. ⟨10.1016/j.immuni.2016.02.025⟩. ⟨hal-02379906⟩

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