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Potent immunogenicity in BRCA1‐mutated patients with high‐grade serous ovarian carcinoma

High‐grade serous ovarian carcinomas (HGSOCs) were among the tumours with an unsatisfactory outcome of immune checkpoint inhibitors (ICIs). It is imperative to develop feasible biomarker for identifying responsive candidates and guiding precise immunotherapy for HGSOC patients. Here, we analysed gen...

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Detalles Bibliográficos
Autores principales: Dai, Ying, Sun, Chengdu, Feng, Yi, Jia, Qingzhu, Zhu, Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050488/
https://www.ncbi.nlm.nih.gov/pubmed/29855141
http://dx.doi.org/10.1111/jcmm.13678
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author Dai, Ying
Sun, Chengdu
Feng, Yi
Jia, Qingzhu
Zhu, Bo
author_facet Dai, Ying
Sun, Chengdu
Feng, Yi
Jia, Qingzhu
Zhu, Bo
author_sort Dai, Ying
collection PubMed
description High‐grade serous ovarian carcinomas (HGSOCs) were among the tumours with an unsatisfactory outcome of immune checkpoint inhibitors (ICIs). It is imperative to develop feasible biomarker for identifying responsive candidates and guiding precise immunotherapy for HGSOC patients. Here, we analysed genomic data of patients with HGSOCs to depict their immunological phenotype of tumour microenvironment (TME) and figure out the major determinants of immunogenicity. In comparison with other solid tumours, we observed the lowest levels of PD‐L1, total mutation burden (TMB) and cytolytic molecules in HGSOCs. Surprisingly, TMB is not certainly positively related to tumour immune response as it failed to predict the response to ICIs in a considerable portion of patients in previous clinical trials. By a machine learning approach in search of biomarkers for immunotherapy implications for HGSOCs, we identified the ten most dominant factors determining the immunogenicity of HGSOCs. Interestingly, we found that BRCA1 mutated tumours presented a potent immunogenic phenotype, independent of TMB, meeting the criteria of both our dominant factors and the determinants of immunogenicity established before. Our findings provide evidence that BRCA1‐mutation may be served as a predictive biomarker in guiding ICI therapies for the patients with HGSOCs.
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spelling pubmed-60504882018-08-01 Potent immunogenicity in BRCA1‐mutated patients with high‐grade serous ovarian carcinoma Dai, Ying Sun, Chengdu Feng, Yi Jia, Qingzhu Zhu, Bo J Cell Mol Med Original Articles High‐grade serous ovarian carcinomas (HGSOCs) were among the tumours with an unsatisfactory outcome of immune checkpoint inhibitors (ICIs). It is imperative to develop feasible biomarker for identifying responsive candidates and guiding precise immunotherapy for HGSOC patients. Here, we analysed genomic data of patients with HGSOCs to depict their immunological phenotype of tumour microenvironment (TME) and figure out the major determinants of immunogenicity. In comparison with other solid tumours, we observed the lowest levels of PD‐L1, total mutation burden (TMB) and cytolytic molecules in HGSOCs. Surprisingly, TMB is not certainly positively related to tumour immune response as it failed to predict the response to ICIs in a considerable portion of patients in previous clinical trials. By a machine learning approach in search of biomarkers for immunotherapy implications for HGSOCs, we identified the ten most dominant factors determining the immunogenicity of HGSOCs. Interestingly, we found that BRCA1 mutated tumours presented a potent immunogenic phenotype, independent of TMB, meeting the criteria of both our dominant factors and the determinants of immunogenicity established before. Our findings provide evidence that BRCA1‐mutation may be served as a predictive biomarker in guiding ICI therapies for the patients with HGSOCs. John Wiley and Sons Inc. 2018-05-31 2018-08 /pmc/articles/PMC6050488/ /pubmed/29855141 http://dx.doi.org/10.1111/jcmm.13678 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Dai, Ying
Sun, Chengdu
Feng, Yi
Jia, Qingzhu
Zhu, Bo
Potent immunogenicity in BRCA1‐mutated patients with high‐grade serous ovarian carcinoma
title Potent immunogenicity in BRCA1‐mutated patients with high‐grade serous ovarian carcinoma
title_full Potent immunogenicity in BRCA1‐mutated patients with high‐grade serous ovarian carcinoma
title_fullStr Potent immunogenicity in BRCA1‐mutated patients with high‐grade serous ovarian carcinoma
title_full_unstemmed Potent immunogenicity in BRCA1‐mutated patients with high‐grade serous ovarian carcinoma
title_short Potent immunogenicity in BRCA1‐mutated patients with high‐grade serous ovarian carcinoma
title_sort potent immunogenicity in brca1‐mutated patients with high‐grade serous ovarian carcinoma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050488/
https://www.ncbi.nlm.nih.gov/pubmed/29855141
http://dx.doi.org/10.1111/jcmm.13678
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