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Natural Killer Cells: the Missing Link in Effective Treatment for High-Grade Serous Ovarian Carcinoma

  • Gynecologic Cancers (JS Ferriss, Section Editor)
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Opinion statement

Ovarian cancer (OC), especially high-grade serous cancer (HGSC), is a highly heterogeneous malignancy with limited options for curative treatment and a high frequency of relapse. Interactions between OC and the immune system may permit immunoediting and immune escape, and current standard of care therapies can influence immune cell infiltration and function within the tumor microenvironment. Natural killer (NK) cells are involved in cancer immunosurveillance and immunoediting and can be activated by therapy, but deliberate approaches to maximize NK cell reactivity for treatment of HGSC are in their infancy. NK cells may be the ideal target for immunotherapy of HGSC. The diverse functions of NK cells, and their established roles in immunosurveillance, make them attractive candidates for more precise and effective HGSC treatment. NK cells’ functional capabilities differ because of variation in receptor expression and genetics, with meaningful impacts on their anticancer activity. Studying HGSC:NK cell interactions will define the features that predict the best outcomes for patients with the disease, but the highly diverse nature of HGSC will likely require combination therapies or approaches to simultaneously target multiple, co-existing features of the tumor to avoid tumor escape and relapse. We expect that the ideal therapy will enable NK cell infiltration and activity, reverse immunosuppression within the tumor microenvironment, and enable effector functions against the diverse subpopulations that comprise HGSC.

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Acknowledgements

We gratefully acknowledge Designs that Cell for assistance with our figure. The Dalhousie University is located in Mi’kma’ki, the ancestral and unceded territory of the Mi’kmaq.

Funding

This research was supported by a Terry Fox Research Institute New Investigator award to JEB within the pan-Canadian Immunotherapeutic Network, and research funding from Ovarian Cancer Canada to JEB and BML. SN and MPT are trainees in the Cancer Research Training Program of the Beatrice Hunter Cancer Research Institute, with funds for MPT provided by the Bruce and Dorothy Rosetti Endowment through the Dalhousie Medical Research Foundation. MPT is supported by a Nova Scotia Graduate Scholarship. BioCanRx, a Canadian Network of Centres of Excellence, provided funding support for this research to APN. SN is supported by a Killam Scholarship, the President’s award from Dalhousie University and a CIHR Vanier Scholarship.

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  1. Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada

    Morgan Pugh-Toole BSc, Brendan M. Leung PhD & Jeanette E. Boudreau

  2. Beatrice Hunter Cancer Research Institute, Halifax, Nova Scotia, Canada

    Morgan Pugh-Toole BSc, Sarah Nersesian BSc, MSc, Brendan M. Leung PhD & Jeanette E. Boudreau

  3. Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, Ontario, Canada

    Anna P. Nicolela

  4. Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, B3H 4R5, Canada

    Sarah Nersesian BSc, MSc & Jeanette E. Boudreau

  5. School of Biomedical Engineering, Dalhousie University, Halifax, Nova Scotia, Canada

    Brendan M. Leung PhD

  6. Department of Applied Oral Sciences, Dalhousie University, Halifax, Nova Scotia, Canada

    Brendan M. Leung PhD

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  1. Morgan Pugh-Toole BSc
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Pugh-Toole, M., Nicolela, A.P., Nersesian, S. et al. Natural Killer Cells: the Missing Link in Effective Treatment for High-Grade Serous Ovarian Carcinoma. Curr. Treat. Options in Oncol. 23, 210–226 (2022). https://doi.org/10.1007/s11864-021-00929-x

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