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Translational Therapeutics

Immuno-genomic characterisation of high-grade serous ovarian cancer reveals immune evasion mechanisms and identifies an immunological subtype with a favourable prognosis and improved therapeutic efficacy

British Journal of Cancer volume 126, pages 1570–1580 (2022)Cite this article

Subjects

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.

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Fig. 1: Functional characterisation of prognostic genes.
Fig. 2: The landscape of the tumour immune microenvironment.
Fig. 3: Genomic states associated with the immunological phenotypes.
Fig. 4: Tumour immunogenicity is associated with the different immunological phenotypes.
Fig. 5: Chemotherapy modulates the immune microenvironment of HGSOC tumours.
Fig. 6: The interplay between immunophenotypes and intrinsic molecular subtypes.

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Data availability

The datasets used and/or analysed during the present study are available from the corresponding author on reasonable request.

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Funding

This study was supported by the Zhejiang Provincial Natural Science Foundation of China (Grant No. LY22C060001). The funders had no roles in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Author notes

  1. These authors contributed equally: Jie Sun, Congcong Yan, Dandan Xu.

Authors and Affiliations

  1. School of Biomedical Engineering, Wenzhou Medical University, 325027, Wenzhou, P. R. China

    Jie Sun, Congcong Yan, Zicheng Zhang, Ke Li & Meng Zhou

  2. Centre for Addiction and Mental Health, Toronto, ON, Canada

    Dandan Xu

  3. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Dandan Xu

  4. Department of Pathology, Harbin Medical University, 150081, Harbin, P. R. China

    Xiaobo Li & Dapeng Hao

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  1. Jie Sun
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Contributions

MZ and DPH conceived and designed the study. JS, DPH, CCY, DDX, ZCZ and KL prepared and carried out all analyses, including the development of their statistical framework, and interpreting the data. XBL collected the patient samples and performed immunohistochemical analysis. MZ and DPH drafted the manuscript. All authors participated in the interpretation and discussion of the results and in the version of the manuscript.

Corresponding authors

Correspondence to Meng Zhou or Dapeng Hao.

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The authors declare no competing interests.

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This study was approved by the Ethics Committee of Harbin Medical University and written informed consent was obtained from all the participants.

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Sun, J., Yan, C., Xu, D. et al. Immuno-genomic characterisation of high-grade serous ovarian cancer reveals immune evasion mechanisms and identifies an immunological subtype with a favourable prognosis and improved therapeutic efficacy. Br J Cancer 126, 1570–1580 (2022). https://doi.org/10.1038/s41416-021-01692-4

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