title: Mutanome and expression of immune response genes in microsatellite stable colon cancer.
abstract: The aim of this study was to analyze the impact of the mutanome in the prognosis of microsatellite stable stage II CRC tumors. The exome of 42 stage II, microsatellite stable, colon tumors (21 of them relapse) and their paired mucosa were sequenced and analyzed. Although some pathways accumulated more mutations in patients exhibiting good or poor prognosis, no single somatic mutation was associated with prognosis. Exome sequencing data is also valuable to infer tumor neoantigens able to elicit a host immune response. Hence, putative neoantigens were identified by combining information about missense mutations in each tumor and HLAs genotypes of the patients. Under the hypothesis that neoantigens should be correctly presented in order to activate the immune response, expression levels of genes involved in the antigen presentation machinery were also assessed. In addition, CD8A level (as a marker of T-cell infiltration) was measured. We found that tumors with better prognosis showed a tendency to generate a higher number of immunogenic epitopes, and up-regulated genes involved in the antigen processing machinery. Moreover, tumors with higher T-cell infiltration also showed better prognosis. Stratifying by consensus molecular subtype, CMS4 tumors showed the highest association of expression levels of genes involved in the antigen presentation machinery with prognosis. Thus, we hypothesize that a subset of stage II microsatellite stable CRC tumors are able to generate an immune response in the host via MHC class I antigen presentation, directly related with a better prognosis.
authors.affiliation: Unit of Biomarkers and Susceptibility, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Sanz-Pamplona
authors.affiliation: Translational Research Laboratory, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Gil-Hoyos
authors.affiliation: Unit of Biomarkers and Susceptibility, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Adriana
authors.initials: A
authors.lastname: López-Doriga
authors.affiliation: Unit of Biomarkers and Susceptibility, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: M Henar
authors.initials: MH
authors.lastname: Alonso
authors.affiliation: Unit of Biomarkers and Susceptibility, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Susanna
authors.initials: S
authors.lastname: Aussó
authors.affiliation: Translational Research Laboratory, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: David G
authors.initials: DG
authors.lastname: Molleví
authors.affiliation: Translational Research Laboratory, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.|Department of Medical Oncology, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Santos
authors.affiliation: Pathology Service, University Hospital Bellvitge (HUB - IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Sanjuán
authors.affiliation: Translational Research Laboratory, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.|Department of Medical Oncology, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Salazar
authors.affiliation: Translational Research Laboratory, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Alemany
authors.affiliation: Unit of Biomarkers and Susceptibility, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L'Hospitalet de Llobregat, Barcelona, Spain.|Department of Clinical Sciences, Faculty of Medicine, University of Barcelona (UB), Barcelona, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Moreno
mesh_terms: D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007110:Immunity, Active / Q000235:genetics; D053842:Microsatellite Instability; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis
keywords: antigen presentation; colorectal cancer; immune response; neoantigens; prognosis