Cancer Immunology, Immunotherapy

, Volume 64, Issue 3, pp 337–347 | Cite as

Activated regulatory and memory T-cells accumulate in malignant ascites from ovarian carcinoma patients

  • Johannes Landskron
  • Øystein Helland
  • Knut Martin Torgersen
  • Einar Martin Aandahl
  • Bjørn Tore Gjertsen
  • Line Bjørge
  • Kjetil Taskén
Original Article

Abstract

Invasive ovarian cancer is associated with poor outcome. The presence of infiltrating regulatory T-cells (Tregs) suppresses protective anti-tumor immune responses, and their accumulation into the tumor microenvironment correlates with reduced survival in ovarian cancer patients. Here, we conducted a detailed characterization of CD4+ T-cells, CD8+ T-cells and Treg subsets in the peripheral blood and malignant ascites fluid from seventeen patients with ovarian carcinoma of epithelial origin. Cell distribution, activation status and proliferation status were assessed by multi-color flow cytometry. In ascites fluid, a significant accumulation of CD8+ cytotoxic T-cells and Tregs was observed compared to peripheral blood. Furthermore, a skewing toward the CD45RA effector/memory compartment was observed in all T-cell subsets in the ascites fluid, but was most pronounced in the Treg population. Regulatory T-cells in the malignant ascites were more activated and had a higher proliferation rate compared to blood-derived cells from the same patient, and their number in ascites was positively correlated with the number of epithelial cells in effusion. In summary, we demonstrate an accumulation of activated CD4+, CD8+ and regulatory T-cells in the cancer microenvironment of ovarian carcinoma.

Keywords

Tumor-infiltrating lymphocytes Regulatory T-cells Ovarian carcinoma Ascites fluid CD147 

Abbreviations

CCL17

Chemokine (C–C motif) ligand 17

CCL22

Chemokine (C–C motive) ligand 22

CCR4

Chemokine (C–C motive) receptor 4

CTLA4

Cytotoxic T-lymphocyte-associated protein 4

EpCAM

Epithelial cell adhesion molecule

FIGO

International Federation of Gynaecology and Obstetrics

FoxP3

Forkhead box P3

IDO

Indoleamine 2,3-dioxygenase

Ki-67

Marker of proliferation Ki-67

MHC

Major histocompatibility complex

PBMC

Peripheral blood mononuclear cells

PBS

Phosphate buffered saline

PD1

Programmed cell death 1

TALs

Tumor-associated lymphocytes

TILs

Tumor-infiltrating lymphocytes

Treg

Regulatory T-cell

Notes

Acknowledgments

We thank the pathologists from the Department of Pathology, The Gade Institute, Haukeland University Hospital, Bergen, Norway for routine histopathological diagnosis of the tumor specimens. Furthermore, we thank Isabelle Cornez, Kristoffer W. Brudvik and Simer J. Bains for help with processing samples for subsequent analysis. This work was supported by the Research Council of Norway, the Norwegian Cancer Society, the Kristian Gerhard Jebsen Foundation and Anders Jahre’s Foundation.

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

262_2014_1636_MOESM1_ESM.pdf (3.1 mb)
Supplementary material 1 (PDF 3213 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Johannes Landskron
    • 1
    • 2
    • 3
  • Øystein Helland
    • 7
    • 8
  • Knut Martin Torgersen
    • 1
    • 10
  • Einar Martin Aandahl
    • 1
    • 2
    • 4
    • 5
  • Bjørn Tore Gjertsen
    • 9
    • 11
  • Line Bjørge
    • 7
    • 8
  • Kjetil Taskén
    • 1
    • 2
    • 3
    • 4
    • 6
  1. 1.Biotechnology Centre of OsloUniversity of OsloOsloNorway
  2. 2.Centre for Molecular Medicine Norway, Nordic EMBL PartnershipUniversity of OsloOsloNorway
  3. 3.K. G. Jebsen Centre for Cancer ImmunotherapyUniversity of Oslo and University Hospital of OsloOsloNorway
  4. 4.K. G. Jebsen Inflammation Research CentreUniversity of Oslo and University Hospital of OsloOsloNorway
  5. 5.Section for Transplantation Surgery and Clinic for Specialized Medicine and SurgeryOslo University Hospital RikshospitaletOsloNorway
  6. 6.Department of Infectious Diseases Clinic for MedicineOslo University HospitalOsloNorway
  7. 7.Department of Obstetrics and GynecologyHaukeland University HospitalBergenNorway
  8. 8.Institute of Clinical Medicine, Institute of Internal MedicineUniversity of BergenBergenNorway
  9. 9.Centre of Cancer Biomarkers CCBIO, Department of Clinical ScienceUniversity of BergenBergenNorway
  10. 10.Oncology Business UnitPfizer ASOsloNorway
  11. 11.Department of Internal Medicine, Hematology SectionHaukeland University HospitalBergenNorway

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