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Myeloid-derived suppressor cells at diagnosis may discriminate between benign and malignant ovarian tumors
  1. An Coosemans1,2,
  2. Thaïs Baert1,3,
  3. Jolien Ceusters1,
  4. Pieter Busschaert4,
  5. Chiara Landolfo1,5,
  6. Tina Verschuere6,
  7. Anne-Sophie Van Rompuy7,
  8. Adriaan Vanderstichele2,4,
  9. Wouter Froyman2,8,
  10. Patrick Neven2,4,
  11. Ben Van Calster8,9,
  12. Ignace Vergote1,2,4 and
  13. Dirk Timmerman2,8
  1. 1 Department of Oncology, Laboratory of Tumor Immunology and Immunotherapy, ImmunOvar Research Group, Katholieke Universiteit Leuven, Leuven, Belgium
  2. 2 Department of Gynecology and Obstetrics, Leuven Cancer Institute, University Hospital Leuven, Leuven, Belgium
  3. 3 Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte gGmbH, Essen, Germany
  4. 4 Department of Oncology, Laboratory of Gynecologic Oncology, Katholieke Universiteit Leuven, Leuven, Belgium
  5. 5 Department of Gynecology and Obstetrics, Queen Charlotte's and Chelsea Hospital, London, UK
  6. 6 European Organisation for Research and Treatment of Cancer, Brussels, Belgium
  7. 7 Department of Pathology, Katholieke Universiteit Leuven, Leuven, Belgium
  8. 8 Department of Development and Regeneration, Women and Child, Katholieke Universiteit Leuven, Leuven, Belgium
  9. 9 Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Dr An Coosemans, Department of Oncology, Laboratory of Tumor Immunology and Immunotherapy, ImmunOvar Research Group, Katholieke Universiteit Leuven, Leuven 3000, Belgium; an.coosemans{at}kuleuven.be

Abstract

Background The behavior of the immune system as a driver in the progression of ovarian cancer has barely been studied. Our knowledge is mainly limited to the intra-tumoral adaptive immune system. Because of the widespread metastases of ovarian cancer, an assessment of the circulating immune system seems more accurate.

To demonstrate the presence of immune cells in blood samples of patients with ovarian neoplasms.

Methods In this exploratory prospective cohort study, peripheral blood mononuclear cells were collected at diagnosis from 143 women, including 62 patients with benign cysts, 13 with borderline tumor, 41 with invasive ovarian cancer, and 27 age-matched healthy controls. Immune profile analyses, based on the presence of CD4 (cluster of differentiation), CD8, natural killer cells, myeloid-derived suppressor cells, and regulatory T cells, were performed by fluorescence activated cell sorting.

Results In a multivariable analysis, six immune cells (activated regulatory T cells, natural killer cells, myeloid-derived suppressor cells, monocytic myeloid-derived suppressor cells, exhausted monocytic myeloid-derived suppressor cells, and total myeloid cells) were selected as independent predictors of malignancy, with an optimism-corrected area under the receiver operating characteristic curve (AUC) of 0.858. In contrast, a profile based on CD8 and regulatory T cells, the current standard in ovarian cancer immunology, resulted in an AUC of 0.639.

Conclusions Our immune profile in blood suggests an involvement of innate immunosuppression driven by myeloid-derived suppressor cells in the development of ovarian cancer. This finding could contribute to clinical management of patients and in selection of immunotherapy.

  • ovarian cancer
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Footnotes

  • Contributors All authors have provided substantial contribution to the study and/or the manuscript and are in agreement will all aspects of the final manuscript.

  • Funding This work was supported by Kom Op Tegen Kanker (Stand Up to Cancer), the Flemish Cancer Society under grant 2016/10728/2603 to AC; the Olivia Fund under grant 2017/LUF/00135 to AC; Amgen Chair for Therapeutic Advances in Ovarian Cancer under grant 2017/LUF/00069 to IV; Internal Funds KU Leuven under grant C24/15/037 to BVC and DT; Research Foundation – Flanders (FWO) under grants G0B4716N to BVC and DT; 12F3114N to AC; 1803415N to DT; 12N4415N to TV; and Linbury Trust Grant under grant LIN2600 to CL.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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