POLE proofreading mutations elicit an anti-tumor immune response in endometrial cancer Running title: POLE mutations and immune response in endometrial cancer Authors:
نویسندگان
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
منابع مشابه
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 کاملBiology 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...
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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.
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Accurate duplication of DNA prior to cell division is essential to suppress mutagenesis and tumour development. The high fidelity of eukaryotic DNA replication is due to a combination of accurate incorporation of nucleotides into the nascent DNA strand by DNA polymerases, the recognition and removal of mispaired nucleotides (proofreading) by the exonuclease activity of DNA polymerases δ and ε, ...
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Immune evasion is a well-recognized hallmark of cancer and recent studies with immunotherapy agents have suggested that tumors with increased numbers of neoantigens elicit greater immune responses. We hypothesized that the immune system presents a common selective pressure on high mutation burden tumors and therefore immune evasion mutations would be enriched in high mutation burden tumors. The...
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تاریخ انتشار 2015