Myeloid-derived suppressor cells at diagnosis may discriminate between benign and malignant ovarian tumors.


Journal

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
ISSN: 1525-1438
Titre abrégé: Int J Gynecol Cancer
Pays: England
ID NLM: 9111626

Informations de publication

Date de publication:
11 2019
Historique:
received: 17 05 2019
revised: 19 07 2019
accepted: 26 07 2019
entrez: 6 11 2019
pubmed: 7 11 2019
medline: 15 4 2020
Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 31685557
pii: ijgc-2019-000521
doi: 10.1136/ijgc-2019-000521
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1381-1388

Informations de copyright

© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

An Coosemans (A)

Department of Oncology, Laboratory of Tumor Immunology and Immunotherapy, ImmunOvar Research Group, Katholieke Universiteit Leuven, Leuven, Belgium an.coosemans@kuleuven.be.
Department of Gynecology and Obstetrics, Leuven Cancer Institute, University Hospital Leuven, Leuven, Belgium.

Thaïs Baert (T)

Department of Oncology, Laboratory of Tumor Immunology and Immunotherapy, ImmunOvar Research Group, Katholieke Universiteit Leuven, Leuven, Belgium.
Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte gGmbH, Essen, Germany.

Jolien Ceusters (J)

Department of Oncology, Laboratory of Tumor Immunology and Immunotherapy, ImmunOvar Research Group, Katholieke Universiteit Leuven, Leuven, Belgium.

Pieter Busschaert (P)

Department of Oncology, Laboratory of Gynecologic Oncology, Katholieke Universiteit Leuven, Leuven, Belgium.

Chiara Landolfo (C)

Department of Oncology, Laboratory of Tumor Immunology and Immunotherapy, ImmunOvar Research Group, Katholieke Universiteit Leuven, Leuven, Belgium.
Department of Gynecology and Obstetrics, Queen Charlotte's and Chelsea Hospital, London, UK.

Tina Verschuere (T)

European Organisation for Research and Treatment of Cancer, Brussels, Belgium.

Anne-Sophie Van Rompuy (AS)

Department of Pathology, Katholieke Universiteit Leuven, Leuven, Belgium.

Adriaan Vanderstichele (A)

Department of Gynecology and Obstetrics, Leuven Cancer Institute, University Hospital Leuven, Leuven, Belgium.
Department of Oncology, Laboratory of Gynecologic Oncology, Katholieke Universiteit Leuven, Leuven, Belgium.

Wouter Froyman (W)

Department of Gynecology and Obstetrics, Leuven Cancer Institute, University Hospital Leuven, Leuven, Belgium.
Department of Development and Regeneration, Women and Child, Katholieke Universiteit Leuven, Leuven, Belgium.

Patrick Neven (P)

Department of Gynecology and Obstetrics, Leuven Cancer Institute, University Hospital Leuven, Leuven, Belgium.
Department of Oncology, Laboratory of Gynecologic Oncology, Katholieke Universiteit Leuven, Leuven, Belgium.

Ben Van Calster (B)

Department of Development and Regeneration, Women and Child, Katholieke Universiteit Leuven, Leuven, Belgium.
Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.

Ignace Vergote (I)

Department of Oncology, Laboratory of Tumor Immunology and Immunotherapy, ImmunOvar Research Group, Katholieke Universiteit Leuven, Leuven, Belgium.
Department of Gynecology and Obstetrics, Leuven Cancer Institute, University Hospital Leuven, Leuven, Belgium.
Department of Oncology, Laboratory of Gynecologic Oncology, Katholieke Universiteit Leuven, Leuven, Belgium.

Dirk Timmerman (D)

Department of Gynecology and Obstetrics, Leuven Cancer Institute, University Hospital Leuven, Leuven, Belgium.
Department of Development and Regeneration, Women and Child, Katholieke Universiteit Leuven, Leuven, Belgium.

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