Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability.
Identifieur interne : 000051 ( France/Analysis ); précédent : 000050; suivant : 000052Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability.
Auteurs : Bernhard Mlecnik [France] ; Gabriela Bindea [France] ; Helen K. Angell [Royaume-Uni] ; Pauline Maby [France] ; Mihaela Angelova [Autriche] ; David Tougeron [France] ; Sarah E. Church [France] ; Lucie Lafontaine [France] ; Maria Fischer [Autriche] ; Tessa Fredriksen [France] ; Maristella Sasso [France] ; Amélie M. Bilocq [France] ; Amos Kirilovsky [France] ; Anna C. Obenauf [Autriche] ; Mohamad Hamieh [France] ; Anne Berger [France] ; Patrick Bruneval [France] ; Jean-Jacques Tuech [France] ; Jean-Christophe Sabourin [France] ; Florence Le Pessot [France] ; Jacques Mauillon [France] ; Arash Rafii [Qatar] ; Pierre Laurent-Puig [France] ; Michael R. Speicher [Autriche] ; Zlatko Trajanoski [Autriche] ; Pierre Michel [France] ; Richard Sesboüe [France] ; Thierry Frebourg [France] ; Franck Pagès [France] ; Viia Valge-Archer [Royaume-Uni] ; Jean-Baptiste Latouche [France] ; Jérôme Galon [France]Source :
- Immunity [ 1097-4180 ] ; 2016.
English descriptors
- KwdEn :
- Aged, Aged, 80 and over, Cells, Cultured, Colorectal Neoplasms (diagnosis), Colorectal Neoplasms (mortality), Cytotoxicity Tests, Immunologic, DNA Mutational Analysis, Female, Frameshift Mutation (genetics), Humans, Immunoassay (methods), Immunologic Memory, Male, Microsatellite Instability, Microsatellite Repeats, Pathology, Molecular (methods), Predictive Value of Tests, Prognosis, Survival Analysis, T-Lymphocyte Subsets (immunology), Th1 Cells (immunology), Transcriptome.
- MESH :
- diagnosis : Colorectal Neoplasms.
- genetics : Frameshift Mutation.
- immunology : T-Lymphocyte Subsets, Th1 Cells.
- methods : Immunoassay, Pathology, Molecular.
- mortality : Colorectal Neoplasms.
- Aged, Aged, 80 and over, Cells, Cultured, Cytotoxicity Tests, Immunologic, DNA Mutational Analysis, Female, Humans, Immunologic Memory, Male, Microsatellite Instability, Microsatellite Repeats, Predictive Value of Tests, Prognosis, Survival Analysis, Transcriptome.
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.
DOI: 10.1016/j.immuni.2016.02.025
PubMed: 26982367
Affiliations:
- Autriche, France, Qatar, Royaume-Uni
- Haute-Normandie, Région Normandie, Île-de-France
- Le Havre, Paris, Rouen
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pubmed:26982367Le document en format XML
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Bilocq</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Kirilovsky, Amos" sort="Kirilovsky, Amos" uniqKey="Kirilovsky A" first="Amos" last="Kirilovsky">Amos Kirilovsky</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Obenauf, Anna C" sort="Obenauf, Anna C" uniqKey="Obenauf A" first="Anna C" last="Obenauf">Anna C. Obenauf</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Human Genetics, Medical University of Graz, 8010 Graz, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Institute of Human Genetics, Medical University of Graz, 8010 Graz</wicri:regionArea><wicri:noRegion>8010 Graz</wicri:noRegion></affiliation></author><author><name sortKey="Hamieh, Mohamad" sort="Hamieh, Mohamad" uniqKey="Hamieh M" first="Mohamad" last="Hamieh">Mohamad Hamieh</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation></author><author><name sortKey="Berger, Anne" sort="Berger, Anne" uniqKey="Berger A" first="Anne" last="Berger">Anne Berger</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; Department of General and Digestive Surgery, Hôpital Européen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, 75015 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; Department of General and Digestive Surgery, Hôpital Européen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, 75015 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Bruneval, Patrick" sort="Bruneval, Patrick" uniqKey="Bruneval P" first="Patrick" last="Bruneval">Patrick Bruneval</name><affiliation wicri:level="3"><nlm:affiliation>Department of Anatomopathology, Hôpital Européen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, 75015 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Anatomopathology, Hôpital Européen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, 75015 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Tuech, Jean Jacques" sort="Tuech, Jean Jacques" uniqKey="Tuech J" first="Jean-Jacques" last="Tuech">Jean-Jacques Tuech</name><affiliation wicri:level="3"><nlm:affiliation>Department of Digestive Surgery, Rouen University Hospital, 76000 Rouen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Digestive Surgery, Rouen University Hospital, 76000 Rouen</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation></author><author><name sortKey="Sabourin, Jean Christophe" sort="Sabourin, Jean Christophe" uniqKey="Sabourin J" first="Jean-Christophe" last="Sabourin">Jean-Christophe Sabourin</name><affiliation wicri:level="3"><nlm:affiliation>Department of Anatomopathology, Rouen University Hospital, 76000 Rouen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Anatomopathology, Rouen University Hospital, 76000 Rouen</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation></author><author><name sortKey="Le Pessot, Florence" sort="Le Pessot, Florence" uniqKey="Le Pessot F" first="Florence" last="Le Pessot">Florence Le Pessot</name><affiliation wicri:level="3"><nlm:affiliation>Department of Anatomopathology, Rouen University Hospital, 76000 Rouen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Anatomopathology, Rouen University Hospital, 76000 Rouen</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation></author><author><name sortKey="Mauillon, Jacques" sort="Mauillon, Jacques" uniqKey="Mauillon J" first="Jacques" last="Mauillon">Jacques Mauillon</name><affiliation wicri:level="3"><nlm:affiliation>Department of Anatomopathology, Rouen University Hospital, 76000 Rouen, France; Department of Gastroenterology, Le Havre Hospital, 76600 Le Havre, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Anatomopathology, Rouen University Hospital, 76000 Rouen, France; Department of Gastroenterology, Le Havre Hospital, 76600 Le Havre</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region><settlement type="city">Le Havre</settlement></placeName></affiliation></author><author><name sortKey="Rafii, Arash" sort="Rafii, Arash" uniqKey="Rafii A" first="Arash" last="Rafii">Arash Rafii</name><affiliation wicri:level="1"><nlm:affiliation>Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, 3263 Doha, Qatar.</nlm:affiliation><country xml:lang="fr">Qatar</country><wicri:regionArea>Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, 3263 Doha</wicri:regionArea><wicri:noRegion>3263 Doha</wicri:noRegion></affiliation></author><author><name sortKey="Laurent Puig, Pierre" sort="Laurent Puig, Pierre" uniqKey="Laurent Puig P" first="Pierre" last="Laurent-Puig">Pierre Laurent-Puig</name><affiliation wicri:level="3"><nlm:affiliation>UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; INSERM, UMRS775, Bases Moléculaires de la Réponse aux Xénobiotiques, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; INSERM, UMRS775, Bases Moléculaires de la Réponse aux Xénobiotiques, 75006 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Speicher, Michael R" sort="Speicher, Michael R" uniqKey="Speicher M" first="Michael R" last="Speicher">Michael R. Speicher</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Human Genetics, Medical University of Graz, 8010 Graz, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Institute of Human Genetics, Medical University of Graz, 8010 Graz</wicri:regionArea><wicri:noRegion>8010 Graz</wicri:noRegion></affiliation></author><author><name sortKey="Trajanoski, Zlatko" sort="Trajanoski, Zlatko" uniqKey="Trajanoski Z" first="Zlatko" last="Trajanoski">Zlatko Trajanoski</name><affiliation wicri:level="1"><nlm:affiliation>Biocenter, Division of Bioinformatics, Innsbruck Medical University, 6020 Innsbruck, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Biocenter, Division of Bioinformatics, Innsbruck Medical University, 6020 Innsbruck</wicri:regionArea><wicri:noRegion>6020 Innsbruck</wicri:noRegion></affiliation></author><author><name sortKey="Michel, Pierre" sort="Michel, Pierre" uniqKey="Michel P" first="Pierre" last="Michel">Pierre Michel</name><affiliation wicri:level="3"><nlm:affiliation>Department of Gastroenterology, Rouen University Hospital, 76000 Rouen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Gastroenterology, Rouen University Hospital, 76000 Rouen</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation></author><author><name sortKey="Sesboue, Richard" sort="Sesboue, Richard" uniqKey="Sesboue R" first="Richard" last="Sesboüe">Richard Sesboüe</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation></author><author><name sortKey="Frebourg, Thierry" sort="Frebourg, Thierry" uniqKey="Frebourg T" first="Thierry" last="Frebourg">Thierry Frebourg</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen, France; INSERM, UMRS775, Bases Moléculaires de la Réponse aux Xénobiotiques, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen, France; INSERM, UMRS775, Bases Moléculaires de la Réponse aux Xénobiotiques, 75006 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Pages, Franck" sort="Pages, Franck" uniqKey="Pages F" first="Franck" last="Pagès">Franck Pagès</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France; Department of Immunology, Hôpital Européen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, 75015 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France; Department of Immunology, Hôpital Européen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, 75015 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Valge Archer, Viia" sort="Valge Archer, Viia" uniqKey="Valge Archer V" first="Viia" last="Valge-Archer">Viia Valge-Archer</name><affiliation wicri:level="1"><nlm:affiliation>Innovative Medicines and Early Development, Oncology, AstraZeneca, CB4 OWG Cambridge, UK; MedImmune, CB21 GGH Cambridge, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Innovative Medicines and Early Development, Oncology, AstraZeneca, CB4 OWG Cambridge, UK; MedImmune, CB21 GGH Cambridge</wicri:regionArea><wicri:noRegion>CB21 GGH Cambridge</wicri:noRegion></affiliation></author><author><name sortKey="Latouche, Jean Baptiste" sort="Latouche, Jean Baptiste" uniqKey="Latouche J" first="Jean-Baptiste" last="Latouche">Jean-Baptiste Latouche</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen, France; Department of Genetics, Rouen University Hospital, 76000 Rouen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen, France; Department of Genetics, Rouen University Hospital, 76000 Rouen</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation></author><author><name sortKey="Galon, Jerome" sort="Galon, Jerome" uniqKey="Galon J" first="Jérôme" last="Galon">Jérôme Galon</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France. Electronic address: jerome.galon@crc.jussieu.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26982367</idno><idno type="pmid">26982367</idno><idno type="doi">10.1016/j.immuni.2016.02.025</idno><idno type="wicri:Area/PubMed/Corpus">000050</idno><idno type="wicri:Area/PubMed/Curation">000050</idno><idno type="wicri:Area/PubMed/Checkpoint">000050</idno><idno type="wicri:Area/Ncbi/Merge">000527</idno><idno type="wicri:Area/Ncbi/Curation">000527</idno><idno type="wicri:Area/Ncbi/Checkpoint">000527</idno><idno type="wicri:Area/Main/Merge">000052</idno><idno type="wicri:Area/Main/Curation">000053</idno><idno type="wicri:Area/Main/Exploration">000053</idno><idno type="wicri:Area/France/Extraction">000051</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability.</title><author><name sortKey="Mlecnik, Bernhard" sort="Mlecnik, Bernhard" uniqKey="Mlecnik B" first="Bernhard" last="Mlecnik">Bernhard Mlecnik</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Bindea, Gabriela" sort="Bindea, Gabriela" uniqKey="Bindea G" first="Gabriela" last="Bindea">Gabriela Bindea</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Angell, Helen K" sort="Angell, Helen K" uniqKey="Angell H" first="Helen K" last="Angell">Helen K. Angell</name><affiliation wicri:level="1"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France; Innovative Medicines and Early Development, Oncology, AstraZeneca, CB4 OWG Cambridge, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France; Innovative Medicines and Early Development, Oncology, AstraZeneca, CB4 OWG Cambridge</wicri:regionArea><wicri:noRegion>CB4 OWG Cambridge</wicri:noRegion></affiliation></author><author><name sortKey="Maby, Pauline" sort="Maby, Pauline" uniqKey="Maby P" first="Pauline" last="Maby">Pauline Maby</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France; INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France; INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation></author><author><name sortKey="Angelova, Mihaela" sort="Angelova, Mihaela" uniqKey="Angelova M" first="Mihaela" last="Angelova">Mihaela Angelova</name><affiliation wicri:level="1"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France; Biocenter, Division of Bioinformatics, Innsbruck Medical University, 6020 Innsbruck, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France; Biocenter, Division of Bioinformatics, Innsbruck Medical University, 6020 Innsbruck</wicri:regionArea><wicri:noRegion>6020 Innsbruck</wicri:noRegion></affiliation></author><author><name sortKey="Tougeron, David" sort="Tougeron, David" uniqKey="Tougeron D" first="David" last="Tougeron">David Tougeron</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen, France; Department of Gastroenterology, Rouen University Hospital, 76000 Rouen, France; Department of Genetics, Rouen University Hospital, 76000 Rouen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen, France; Department of Gastroenterology, Rouen University Hospital, 76000 Rouen, France; Department of Genetics, Rouen University Hospital, 76000 Rouen</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation></author><author><name sortKey="Church, Sarah E" sort="Church, Sarah E" uniqKey="Church S" first="Sarah E" last="Church">Sarah E. Church</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Lafontaine, Lucie" sort="Lafontaine, Lucie" uniqKey="Lafontaine L" first="Lucie" last="Lafontaine">Lucie Lafontaine</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Fischer, Maria" sort="Fischer, Maria" uniqKey="Fischer M" first="Maria" last="Fischer">Maria Fischer</name><affiliation wicri:level="1"><nlm:affiliation>Biocenter, Division of Bioinformatics, Innsbruck Medical University, 6020 Innsbruck, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Biocenter, Division of Bioinformatics, Innsbruck Medical University, 6020 Innsbruck</wicri:regionArea><wicri:noRegion>6020 Innsbruck</wicri:noRegion></affiliation></author><author><name sortKey="Fredriksen, Tessa" sort="Fredriksen, Tessa" uniqKey="Fredriksen T" first="Tessa" last="Fredriksen">Tessa Fredriksen</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Sasso, Maristella" sort="Sasso, Maristella" uniqKey="Sasso M" first="Maristella" last="Sasso">Maristella Sasso</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Bilocq, Amelie M" sort="Bilocq, Amelie M" uniqKey="Bilocq A" first="Amélie M" last="Bilocq">Amélie M. Bilocq</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Kirilovsky, Amos" sort="Kirilovsky, Amos" uniqKey="Kirilovsky A" first="Amos" last="Kirilovsky">Amos Kirilovsky</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Obenauf, Anna C" sort="Obenauf, Anna C" uniqKey="Obenauf A" first="Anna C" last="Obenauf">Anna C. Obenauf</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Human Genetics, Medical University of Graz, 8010 Graz, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Institute of Human Genetics, Medical University of Graz, 8010 Graz</wicri:regionArea><wicri:noRegion>8010 Graz</wicri:noRegion></affiliation></author><author><name sortKey="Hamieh, Mohamad" sort="Hamieh, Mohamad" uniqKey="Hamieh M" first="Mohamad" last="Hamieh">Mohamad Hamieh</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation></author><author><name sortKey="Berger, Anne" sort="Berger, Anne" uniqKey="Berger A" first="Anne" last="Berger">Anne Berger</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; Department of General and Digestive Surgery, Hôpital Européen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, 75015 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; Department of General and Digestive Surgery, Hôpital Européen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, 75015 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Bruneval, Patrick" sort="Bruneval, Patrick" uniqKey="Bruneval P" first="Patrick" last="Bruneval">Patrick Bruneval</name><affiliation wicri:level="3"><nlm:affiliation>Department of Anatomopathology, Hôpital Européen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, 75015 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Anatomopathology, Hôpital Européen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, 75015 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Tuech, Jean Jacques" sort="Tuech, Jean Jacques" uniqKey="Tuech J" first="Jean-Jacques" last="Tuech">Jean-Jacques Tuech</name><affiliation wicri:level="3"><nlm:affiliation>Department of Digestive Surgery, Rouen University Hospital, 76000 Rouen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Digestive Surgery, Rouen University Hospital, 76000 Rouen</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation></author><author><name sortKey="Sabourin, Jean Christophe" sort="Sabourin, Jean Christophe" uniqKey="Sabourin J" first="Jean-Christophe" last="Sabourin">Jean-Christophe Sabourin</name><affiliation wicri:level="3"><nlm:affiliation>Department of Anatomopathology, Rouen University Hospital, 76000 Rouen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Anatomopathology, Rouen University Hospital, 76000 Rouen</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation></author><author><name sortKey="Le Pessot, Florence" sort="Le Pessot, Florence" uniqKey="Le Pessot F" first="Florence" last="Le Pessot">Florence Le Pessot</name><affiliation wicri:level="3"><nlm:affiliation>Department of Anatomopathology, Rouen University Hospital, 76000 Rouen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Anatomopathology, Rouen University Hospital, 76000 Rouen</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation></author><author><name sortKey="Mauillon, Jacques" sort="Mauillon, Jacques" uniqKey="Mauillon J" first="Jacques" last="Mauillon">Jacques Mauillon</name><affiliation wicri:level="3"><nlm:affiliation>Department of Anatomopathology, Rouen University Hospital, 76000 Rouen, France; Department of Gastroenterology, Le Havre Hospital, 76600 Le Havre, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Anatomopathology, Rouen University Hospital, 76000 Rouen, France; Department of Gastroenterology, Le Havre Hospital, 76600 Le Havre</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region><settlement type="city">Le Havre</settlement></placeName></affiliation></author><author><name sortKey="Rafii, Arash" sort="Rafii, Arash" uniqKey="Rafii A" first="Arash" last="Rafii">Arash Rafii</name><affiliation wicri:level="1"><nlm:affiliation>Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, 3263 Doha, Qatar.</nlm:affiliation><country xml:lang="fr">Qatar</country><wicri:regionArea>Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, 3263 Doha</wicri:regionArea><wicri:noRegion>3263 Doha</wicri:noRegion></affiliation></author><author><name sortKey="Laurent Puig, Pierre" sort="Laurent Puig, Pierre" uniqKey="Laurent Puig P" first="Pierre" last="Laurent-Puig">Pierre Laurent-Puig</name><affiliation wicri:level="3"><nlm:affiliation>UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; INSERM, UMRS775, Bases Moléculaires de la Réponse aux Xénobiotiques, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; INSERM, UMRS775, Bases Moléculaires de la Réponse aux Xénobiotiques, 75006 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Speicher, Michael R" sort="Speicher, Michael R" uniqKey="Speicher M" first="Michael R" last="Speicher">Michael R. Speicher</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Human Genetics, Medical University of Graz, 8010 Graz, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Institute of Human Genetics, Medical University of Graz, 8010 Graz</wicri:regionArea><wicri:noRegion>8010 Graz</wicri:noRegion></affiliation></author><author><name sortKey="Trajanoski, Zlatko" sort="Trajanoski, Zlatko" uniqKey="Trajanoski Z" first="Zlatko" last="Trajanoski">Zlatko Trajanoski</name><affiliation wicri:level="1"><nlm:affiliation>Biocenter, Division of Bioinformatics, Innsbruck Medical University, 6020 Innsbruck, Austria.</nlm:affiliation><country xml:lang="fr">Autriche</country><wicri:regionArea>Biocenter, Division of Bioinformatics, Innsbruck Medical University, 6020 Innsbruck</wicri:regionArea><wicri:noRegion>6020 Innsbruck</wicri:noRegion></affiliation></author><author><name sortKey="Michel, Pierre" sort="Michel, Pierre" uniqKey="Michel P" first="Pierre" last="Michel">Pierre Michel</name><affiliation wicri:level="3"><nlm:affiliation>Department of Gastroenterology, Rouen University Hospital, 76000 Rouen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Gastroenterology, Rouen University Hospital, 76000 Rouen</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation></author><author><name sortKey="Sesboue, Richard" sort="Sesboue, Richard" uniqKey="Sesboue R" first="Richard" last="Sesboüe">Richard Sesboüe</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation></author><author><name sortKey="Frebourg, Thierry" sort="Frebourg, Thierry" uniqKey="Frebourg T" first="Thierry" last="Frebourg">Thierry Frebourg</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen, France; INSERM, UMRS775, Bases Moléculaires de la Réponse aux Xénobiotiques, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen, France; INSERM, UMRS775, Bases Moléculaires de la Réponse aux Xénobiotiques, 75006 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Pages, Franck" sort="Pages, Franck" uniqKey="Pages F" first="Franck" last="Pagès">Franck Pagès</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France; Department of Immunology, Hôpital Européen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, 75015 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France; Department of Immunology, Hôpital Européen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, 75015 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Valge Archer, Viia" sort="Valge Archer, Viia" uniqKey="Valge Archer V" first="Viia" last="Valge-Archer">Viia Valge-Archer</name><affiliation wicri:level="1"><nlm:affiliation>Innovative Medicines and Early Development, Oncology, AstraZeneca, CB4 OWG Cambridge, UK; MedImmune, CB21 GGH Cambridge, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Innovative Medicines and Early Development, Oncology, AstraZeneca, CB4 OWG Cambridge, UK; MedImmune, CB21 GGH Cambridge</wicri:regionArea><wicri:noRegion>CB21 GGH Cambridge</wicri:noRegion></affiliation></author><author><name sortKey="Latouche, Jean Baptiste" sort="Latouche, Jean Baptiste" uniqKey="Latouche J" first="Jean-Baptiste" last="Latouche">Jean-Baptiste Latouche</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen, France; Department of Genetics, Rouen University Hospital, 76000 Rouen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U1079, Faculté de Médecine, Université de Rouen and the Institute for Research and Innovation in Biomedecine (IRIB), 76000 Rouen, France; Department of Genetics, Rouen University Hospital, 76000 Rouen</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation></author><author><name sortKey="Galon, Jerome" sort="Galon, Jerome" uniqKey="Galon J" first="Jérôme" last="Galon">Jérôme Galon</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris, France. Electronic address: jerome.galon@crc.jussieu.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS1138, Laboratory of Integrative Cancer Immunology, 75006 Paris, France; UMRS1138, Université Paris Descartes - Sorbonne Paris Cité, 75006 Paris, France; UMRS1138, Pierre and Marie Curie University (Paris 6) - Sorbonne Paris Cité, Centre de Recherche des Cordeliers, 75006 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></analytic><series><title level="j">Immunity</title><idno type="eISSN">1097-4180</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Cells, Cultured</term><term>Colorectal Neoplasms (diagnosis)</term><term>Colorectal Neoplasms (mortality)</term><term>Cytotoxicity Tests, Immunologic</term><term>DNA Mutational Analysis</term><term>Female</term><term>Frameshift Mutation (genetics)</term><term>Humans</term><term>Immunoassay (methods)</term><term>Immunologic Memory</term><term>Male</term><term>Microsatellite Instability</term><term>Microsatellite Repeats</term><term>Pathology, Molecular (methods)</term><term>Predictive Value of Tests</term><term>Prognosis</term><term>Survival Analysis</term><term>T-Lymphocyte Subsets (immunology)</term><term>Th1 Cells (immunology)</term><term>Transcriptome</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Colorectal Neoplasms</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Frameshift Mutation</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>T-Lymphocyte Subsets</term><term>Th1 Cells</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Immunoassay</term><term>Pathology, Molecular</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Colorectal Neoplasms</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Cells, Cultured</term><term>Cytotoxicity Tests, Immunologic</term><term>DNA Mutational Analysis</term><term>Female</term><term>Humans</term><term>Immunologic Memory</term><term>Male</term><term>Microsatellite Instability</term><term>Microsatellite Repeats</term><term>Predictive Value of Tests</term><term>Prognosis</term><term>Survival Analysis</term><term>Transcriptome</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Autriche</li><li>France</li><li>Qatar</li><li>Royaume-Uni</li></country><region><li>Haute-Normandie</li><li>Région Normandie</li><li>Île-de-France</li></region><settlement><li>Le Havre</li><li>Paris</li><li>Rouen</li></settlement></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Mlecnik, Bernhard" sort="Mlecnik, Bernhard" uniqKey="Mlecnik B" first="Bernhard" last="Mlecnik">Bernhard Mlecnik</name></region><name sortKey="Berger, Anne" sort="Berger, Anne" uniqKey="Berger A" first="Anne" last="Berger">Anne Berger</name><name sortKey="Bilocq, Amelie M" sort="Bilocq, Amelie M" uniqKey="Bilocq A" first="Amélie M" last="Bilocq">Amélie M. Bilocq</name><name sortKey="Bindea, Gabriela" sort="Bindea, Gabriela" uniqKey="Bindea G" first="Gabriela" last="Bindea">Gabriela Bindea</name><name sortKey="Bruneval, Patrick" sort="Bruneval, Patrick" uniqKey="Bruneval P" first="Patrick" last="Bruneval">Patrick Bruneval</name><name sortKey="Church, Sarah E" sort="Church, Sarah E" uniqKey="Church S" first="Sarah E" last="Church">Sarah E. Church</name><name sortKey="Frebourg, Thierry" sort="Frebourg, Thierry" uniqKey="Frebourg T" first="Thierry" last="Frebourg">Thierry Frebourg</name><name sortKey="Fredriksen, Tessa" sort="Fredriksen, Tessa" uniqKey="Fredriksen T" first="Tessa" last="Fredriksen">Tessa Fredriksen</name><name sortKey="Galon, Jerome" sort="Galon, Jerome" uniqKey="Galon J" first="Jérôme" last="Galon">Jérôme Galon</name><name sortKey="Hamieh, Mohamad" sort="Hamieh, Mohamad" uniqKey="Hamieh M" first="Mohamad" last="Hamieh">Mohamad Hamieh</name><name sortKey="Kirilovsky, Amos" sort="Kirilovsky, Amos" uniqKey="Kirilovsky A" first="Amos" last="Kirilovsky">Amos Kirilovsky</name><name sortKey="Lafontaine, Lucie" sort="Lafontaine, Lucie" uniqKey="Lafontaine L" first="Lucie" last="Lafontaine">Lucie Lafontaine</name><name sortKey="Latouche, Jean Baptiste" sort="Latouche, Jean Baptiste" uniqKey="Latouche J" first="Jean-Baptiste" last="Latouche">Jean-Baptiste Latouche</name><name sortKey="Laurent Puig, Pierre" sort="Laurent Puig, Pierre" uniqKey="Laurent Puig P" first="Pierre" last="Laurent-Puig">Pierre Laurent-Puig</name><name sortKey="Le Pessot, Florence" sort="Le Pessot, Florence" uniqKey="Le Pessot F" first="Florence" last="Le Pessot">Florence Le Pessot</name><name sortKey="Maby, Pauline" sort="Maby, Pauline" uniqKey="Maby P" first="Pauline" last="Maby">Pauline Maby</name><name sortKey="Mauillon, Jacques" sort="Mauillon, Jacques" uniqKey="Mauillon J" first="Jacques" last="Mauillon">Jacques Mauillon</name><name sortKey="Michel, Pierre" sort="Michel, Pierre" uniqKey="Michel P" first="Pierre" last="Michel">Pierre Michel</name><name sortKey="Pages, Franck" sort="Pages, Franck" uniqKey="Pages F" first="Franck" last="Pagès">Franck Pagès</name><name sortKey="Sabourin, Jean Christophe" sort="Sabourin, Jean Christophe" uniqKey="Sabourin J" first="Jean-Christophe" last="Sabourin">Jean-Christophe Sabourin</name><name sortKey="Sasso, Maristella" sort="Sasso, Maristella" uniqKey="Sasso M" first="Maristella" last="Sasso">Maristella Sasso</name><name sortKey="Sesboue, Richard" sort="Sesboue, Richard" uniqKey="Sesboue R" first="Richard" last="Sesboüe">Richard Sesboüe</name><name sortKey="Tougeron, David" sort="Tougeron, David" uniqKey="Tougeron D" first="David" last="Tougeron">David Tougeron</name><name sortKey="Tuech, Jean Jacques" sort="Tuech, Jean Jacques" uniqKey="Tuech J" first="Jean-Jacques" last="Tuech">Jean-Jacques Tuech</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Angell, Helen K" sort="Angell, Helen K" uniqKey="Angell H" first="Helen K" last="Angell">Helen K. Angell</name></noRegion><name sortKey="Valge Archer, Viia" sort="Valge Archer, Viia" uniqKey="Valge Archer V" first="Viia" last="Valge-Archer">Viia Valge-Archer</name></country><country name="Autriche"><noRegion><name sortKey="Angelova, Mihaela" sort="Angelova, Mihaela" uniqKey="Angelova M" first="Mihaela" last="Angelova">Mihaela Angelova</name></noRegion><name sortKey="Fischer, Maria" sort="Fischer, Maria" uniqKey="Fischer M" first="Maria" last="Fischer">Maria Fischer</name><name sortKey="Obenauf, Anna C" sort="Obenauf, Anna C" uniqKey="Obenauf A" first="Anna C" last="Obenauf">Anna C. Obenauf</name><name sortKey="Speicher, Michael R" sort="Speicher, Michael R" uniqKey="Speicher M" first="Michael R" last="Speicher">Michael R. Speicher</name><name sortKey="Trajanoski, Zlatko" sort="Trajanoski, Zlatko" uniqKey="Trajanoski Z" first="Zlatko" last="Trajanoski">Zlatko Trajanoski</name></country><country name="Qatar"><noRegion><name sortKey="Rafii, Arash" sort="Rafii, Arash" uniqKey="Rafii A" first="Arash" last="Rafii">Arash Rafii</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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