Jie Sun1, Congcong Yan1, Dandan Xu2,3, Zicheng Zhang1, Ke Li1, Xiaobo Li4, Meng Zhou5, Dapeng Hao6. 1. School of Biomedical Engineering, Wenzhou Medical University, 325027, Wenzhou, P. R. China. 2. Centre for Addiction and Mental Health, Toronto, ON, Canada. 3. Department of Psychiatry, University of Toronto, Toronto, ON, Canada. 4. Department of Pathology, Harbin Medical University, 150081, Harbin, P. R. China. 5. School of Biomedical Engineering, Wenzhou Medical University, 325027, Wenzhou, P. R. China. zhoumeng@wmu.edu.cn. 6. Department of Pathology, Harbin Medical University, 150081, Harbin, P. R. China. dapeng.hao@gmail.com.
Abstract
BACKGROUND: Immunotherapy has revolutionised the field of cancer therapy and immunology, but has demonstrated limited therapeutic efficacy in high-grade serous ovarian cancer (HGSOC). METHODS: Multi-omics data of 495 TCGA HGSOC tumours and RNA-seq data of 1708 HGSOC tumours were analyzed. Multivariate Cox regression analysis and meta-analyses were used to identify prognostic genes. The immune microenvironment was characterised using the ssGSEA methods for 28 immune cell types. Immunohistochemistry staining of tumour tissues of 14 patients was used to validate the key findings further. RESULTS: A total of 1142 genes were identified as favourable prognostic genes, which are prevailing in immune-related pathways and the infiltration of most immune subpopulations was observed to be associated with a favourable prognosis suggesting that tumour immunogenicity was the most prominent factor associated with improved clinical outcomes and response to chemotherapy of HGSOC. We identified multiple genomic and transcriptomic determinants of immunogenicity, including the copy loss of chromosome 4q and deficiencies of the homologous recombination pathway. Finally, an immunological subtype characterised by increased infiltration of activated CD8 T cells and decreased Tregs was associated with favourable prognosis and improved therapeutic efficacy. CONCLUSIONS: Our study characterised the immunogenomic landscape and refined the immunological classifications of HGSOC. This may improve the selection of patients with HGSOC who are suitable candidates for immunotherapy.
BACKGROUND: Immunotherapy has revolutionised the field of cancer therapy and immunology, but has demonstrated limited therapeutic efficacy in high-grade serous ovarian cancer (HGSOC). METHODS: Multi-omics data of 495 TCGA HGSOC tumours and RNA-seq data of 1708 HGSOC tumours were analyzed. Multivariate Cox regression analysis and meta-analyses were used to identify prognostic genes. The immune microenvironment was characterised using the ssGSEA methods for 28 immune cell types. Immunohistochemistry staining of tumour tissues of 14 patients was used to validate the key findings further. RESULTS: A total of 1142 genes were identified as favourable prognostic genes, which are prevailing in immune-related pathways and the infiltration of most immune subpopulations was observed to be associated with a favourable prognosis suggesting that tumour immunogenicity was the most prominent factor associated with improved clinical outcomes and response to chemotherapy of HGSOC. We identified multiple genomic and transcriptomic determinants of immunogenicity, including the copy loss of chromosome 4q and deficiencies of the homologous recombination pathway. Finally, an immunological subtype characterised by increased infiltration of activated CD8 T cells and decreased Tregs was associated with favourable prognosis and improved therapeutic efficacy. CONCLUSIONS: Our study characterised the immunogenomic landscape and refined the immunological classifications of HGSOC. This may improve the selection of patients with HGSOC who are suitable candidates for immunotherapy.
Authors: Nicole E James; Morgan Woodman; Payton De La Cruz; Katrin Eurich; Melih Arda Ozsoy; Christoph Schorl; Linda C Hanley; Jennifer R Ribeiro Journal: Front Immunol Date: 2022-09-05 Impact factor: 8.786