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Vol. 84, No. 5, 2013
Issue release date: May 2013
Section title: Clinical Study
Oncology 2013;84:273-283
(DOI:10.1159/000343282)

Chemotherapy ± Cetuximab Modulates Peripheral Immune Responses in Metastatic Colorectal Cancer

Xynos I.D. · Karadima M.L. · Voutsas I.F. · Amptoulach S. · Skopelitis E. · Kosmas C. · Gritzapis A.D. · Tsavaris N.
aImperial Clinical Trials Unit-Cancer, Department of Surgery and Cancer, Charing Cross Hospital, Imperial College London, London, UK; bOncology Unit, Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, and cCancer Immunology and Immunotherapy Center, Saint Savvas Cancer Hospital, Athens, and dDepartment of Medicine, 2nd Division of Medical Oncology, Metaxa Cancer Hospital, Piraeus, Greece

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Article / Publication Details

First-Page Preview
Abstract of Clinical Study

Received: 3/28/2012
Accepted: 9/10/2012
Published online: 2/22/2013

Number of Print Pages: 11
Number of Figures: 2
Number of Tables: 3

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: http://www.karger.com/OCL

Abstract

Objective: To identify changes in peripheral immune responses in patients with metastatic colorectal cancer (mCRC) treated with irinotecan/5-fluorouracil/leucovorin (IFL) alone or in combination with cetuximab (C-IFL). Methods: Peripheral blood mononuclear cells (PBMCs) collected from healthy donors (n = 20) and patients with mCRC receiving treatment with either IFL (n = 30) or C-IFL (n = 30) were tested for cytokine production upon polyclonal stimulation with anti-CD3 monoclonal antibody, T cell proliferation in the autologous mixed lymphocyte reaction (auto-MLR) and T regulatory cell (Treg) frequency. The respective results were evaluated over two treatment cycles and further assessed in relation to response to treatment. Results: PBMCs prior to treatment exhibited significantly lower production of IL-2, IFN-γ, IL-12 and IL-18 cytokines and lower auto-MLR responses, whereas Treg frequency, IL-4, IL-10 cytokines were increased compared to healthy donors. During treatment, IL-2, IFN-γ, IL-12, IL-18 and auto-MLR responses increased, while Treg frequency and IL-10 secretion decreased significantly compared to the baseline. Responders to treatment exhibited a significantly higher increase in IL-2, IFN-γ, IL-12 and IL-18 production and auto-MLR responses, and higher decrease in IL-4, IL-10 secretion and Treg frequency. Among all patient subgroups analysed, responders to C-IFL demonstrated significantly higher increase in auto-MLR responses, IL-12 and IL-18 secretion and higher decrease in Treg frequency. Conclusion: The disturbed immune parameters observed in patients with mCRC at presentation can be significantly improved during treatment with IFL and this effect can be potentiated by the addition of cetuximab. Monitoring of the peripheral immune system function could be used as surrogate marker in predicting treatment-related outcome.


  

Author Contacts

Prof. Nikolas Tsavaris
Oncology Unit, Department of Pathophysiology, Laiko General Hospital
Medical School, National and Kapodistrian University of Athens
Mikras Asias 75 Street, GR-11527 Athens (Greece)
E-Mail tsavari1@otenet.gr

  

Article Information

Received: March 28, 2012
Accepted after revision: September 10, 2012
Published online: February 22, 2013
Number of Print Pages : 11
Number of Figures : 2, Number of Tables : 3, Number of References : 48

  

Publication Details

Oncology (International Journal for Cancer Research and Treatment)

Vol. 84, No. 5, Year 2013 (Cover Date: May 2013)

Journal Editor: Markman M. (Philadelphia, Pa.)
ISSN: 0030-2414 (Print), eISSN: 1423-0232 (Online)

For additional information: http://www.karger.com/OCL


Article / Publication Details

First-Page Preview
Abstract of Clinical Study

Received: 3/28/2012
Accepted: 9/10/2012
Published online: 2/22/2013

Number of Print Pages: 11
Number of Figures: 2
Number of Tables: 3

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: http://www.karger.com/OCL


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