POLE mutations and immune response in endometrial cancer

نویسندگان

  • Inge C van Gool
  • Florine A Eggink
  • Luke Freeman-Mills
  • Ellen Stelloo
  • Emanuele Marchi
  • Marco de Bruyn
  • Claire Palles
  • Remi A Nout
  • Cor D de Kroon
  • Elisabeth M Osse
  • Paul Klenerman
  • Carien L Creutzberg
  • Ian PM Tomlinson
  • Vincent THBM Smit
  • Hans W Nijman
  • Tjalling Bosse
  • David N Church
  • Peter Medawar
چکیده

Affiliations: 1 Department of Pathology, Leiden University Medical Center, Albinusdreef 2, Postbus 9600, 2300 RC Leiden, The Netherlands 2 University of Groningen, University Medical Center Groningen, Department of Obstetrics and Gynecology, PO 30.001 9700 RB Groningen, The Netherlands 3 Molecular and Population Genetics Laboratory, The Wellcome Trust Centre for Human Genetics, University of Oxford. Roosevelt Drive, Oxford, OX3 7BN, UK 4 Immunity Theme, NIHR Oxford Comprehensive Biomedical Research Centre, The Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford, OX1 3SY, UK 5 Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, Postbus 9600, 2300 RC Leiden, The Netherlands 6 Department of Gynecology, Leiden University Medical Center, Albinusdreef 2, Postbus 9600, 2300 RC Leiden, The Netherlands

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

POLE proofreading mutation, immune response and prognosis in endometrial cancer

Endometrial cancers (ECs) with POLE proofreading mutations are typified by ultramutation and excellent prognosis. We investigated whether these were related, and found that POLE-mutant ECs display a robust T cell response that corresponds to an enrichment of antigenic tumor neopeptides. Enhanced immunogenicity may explain the favorable outcome of POLE-mutant ECs.

متن کامل

POLE Proofreading Mutations Elicit an Antitumor Immune Response in Endometrial Cancer.

PURPOSE Recent studies have shown that 7% to 12% of endometrial cancers are ultramutated due to somatic mutation in the proofreading exonuclease domain of the DNA replicase POLE. Interestingly, these tumors have an excellent prognosis. In view of the emerging data linking mutation burden, immune response, and clinical outcome in cancer, we investigated whether POLE-mutant endometrial cancers sh...

متن کامل

Biology of Human Tumors POLE Proofreading Mutations Elicit an Antitumor Immune Response in Endometrial Cancer

Purpose: Recent studies have shown that 7% to 12% of endometrial cancers are ultramutated due to somatic mutation in the proofreading exonuclease domain of the DNA replicase POLE. Interestingly, these tumors have an excellent prognosis. In view of the emerging data linking mutation burden, immune response, and clinical outcome in cancer, we investigatedwhether POLE-mutant endometrial cancers sh...

متن کامل

POLE proofreading mutations elicit an anti-tumor immune response in endometrial cancer Running title: POLE mutations and immune response in endometrial cancer Authors:

Affiliations: 1 Department of Pathology, Leiden University Medical Center, Albinusdreef 2, Postbus 9600, 2300 RC Leiden, The Netherlands 2 University of Groningen, University Medical Center Groningen, Department of Obstetrics and Gynecology, PO 30.001 9700 RB Groningen, The Netherlands 3 Molecular and Population Genetics Laboratory, The Wellcome Trust Centre for Human Genetics, University of Ox...

متن کامل

Immunological profiling of molecularly classified high-risk endometrial cancers identifies POLE-mutant and microsatellite unstable carcinomas as candidates for checkpoint inhibition

High-risk endometrial cancer (EC) is an aggressive disease for which new therapeutic options are needed. Aims of this study were to validate the enhanced immune response in highly mutated ECs and to explore immune profiles in other EC subgroups. We evaluated immune infiltration in 116 high-risk ECs from the TransPORTEC consortium, previously classified into four molecular subtypes: (i) ultramut...

متن کامل

Predicted neoantigen load in non-hypermutated endometrial cancers: Correlation with outcome and tumor-specific genomic alterations

Elevated neoantigen load has been previously correlated with improved outcome and response to immune checkpoint blockade in various tumor types. In endometrial cancer, previous studies of neoantigen load prediction have shown that the hypermutated MSI and POLE-mutated tumors harbor significantly higher predicted neoantigen load compared to the hypomutated CN-low/endometrioid and CN-high/serous-...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2015