Cancer Immunology, Immunotherapy

, Volume 61, Issue 7, pp 1045–1053

Regulatory T-cell-mediated inhibition of antitumor immune responses is associated with clinical outcome in patients with liver metastasis from colorectal cancer

  • Kristoffer Watten Brudvik
  • Karen Henjum
  • Einar Martin Aandahl
  • Bjørn Atle Bjørnbeth
  • Kjetil Taskén
Original article

Abstract

Adaptive regulatory T cells (Tregs) contribute to an immunosuppressive microenvironment in colorectal cancer (CRC). Here, we examined whether the level of Treg-mediated inhibition of antitumor immune responses in patients with metastatic CRC (metCRC) selected for liver resection is associated with clinical outcome. Preoperatively and at follow-ups, we did flow-based phenotyping, examined antitumor immunity using peptides from carcinoembryonic antigen (CEA) protein in the presence or absence of CD4+CD25+CD127dim/− cells (Tregs) and determined cytokine and PGE2 levels in patient blood samples. At 18 months post-surgery, 8 patients were disease free (7 alive and 1 dead of unrelated cause) and 10 had experienced disease recurrence (7 alive and 3 dead of metCRC). Prior to surgery, the patients demonstrated Treg-mediated suppression of TNFα and IFNγ expression that could be perturbed through the PGE2/cAMP pathway and the immune suppression was significantly higher in the group that later developed disease recurrence (P = 0.046). Furthermore, the post-surgery plasma PGE2 levels were related to the clinical outcome (PGE2 levels of 280 ± 47 vs. 704 ± 153 pg/ml (mean ± SEM) for disease free and recurrent disease, respectively). T-cell phenotyping revealed higher frequencies of COX-2+ cells in the patients with recurrent disease. These findings support the notion that the level of Treg-mediated suppression of adaptive antitumor immune responses at the time of surgery may influence later clinical outcome of metCRC and provide valuable prognostic information.

Keywords

Colorectal cancer Liver metastasis Regulatory T cells COX-2 PGE2 

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Kristoffer Watten Brudvik
    • 1
  • Karen Henjum
    • 1
    • 2
  • Einar Martin Aandahl
    • 1
    • 3
  • Bjørn Atle Bjørnbeth
    • 2
  • Kjetil Taskén
    • 1
  1. 1.Centre for Molecular Medicine Norway, Nordic EMBL Partnership and Biotechnology CentreUniversity of OsloOsloNorway
  2. 2.Section for Gastroenterology Surgery, Department of SurgeryOslo University Hospital UllevålOsloNorway
  3. 3.Section for Transplantation SurgeryOslo University Hospital RikshospitaletOsloNorway

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