Oncotarget

Research Papers:

Mutanome and expression of immune response genes in microsatellite stable colon cancer

Rebeca Sanz-Pamplona, Raúl Gil-Hoyos, Adriana López-Doriga, M. Henar Alonso, Susanna Aussó, David G. Molleví, Cristina Santos, Xavier Sanjuán, Ramón Salazar, Ramón Alemany and Víctor Moreno _

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Oncotarget. 2016; 7:17711-17725. https://doi.org/10.18632/oncotarget.7293

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Abstract

Rebeca Sanz-Pamplona1, Raúl Gil-Hoyos2, Adriana López-Doriga1, M. Henar Alonso1, Susanna Aussó1, David G. Molleví2, Cristina Santos2,3, Xavier Sanjuán4, Ramón Salazar2,3, Ramón Alemany2, Víctor Moreno1,5

1Unit of Biomarkers and Susceptibility, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L’Hospitalet de Llobregat, Barcelona, Spain

2Translational Research Laboratory, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain

3Department of Medical Oncology, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain

4Pathology Service, University Hospital Bellvitge (HUB – IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain

5Department of Clinical Sciences, Faculty of Medicine, University of Barcelona (UB), Barcelona, Spain

Correspondence to:

Victor Moreno, e-mail: v.moreno@iconcologia.net

Keywords: colorectal cancer, neoantigens, prognosis, antigen presentation, immune response

Received: December 18, 2015     Accepted: January 26, 2016     Published: February 9, 2016

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.


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