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Potent immunogenicity in BRCA1‐mutated patients with high‐grade serous ovarian carcinoma
Authors:Ying Dai  Chengdu Sun  Yi Feng  Qingzhu Jia  Bo Zhu
Affiliation:Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Abstract: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.
Keywords:   BRCA     high‐grade serous ovarian carcinomas  immune checkpoint inhibitor     TCGA     total tumour burden  tumour microenvironment
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