In vitro immunomodulatory properties of gemcitabine alone and in combination with interferon-alpha

Immunol Lett. 2015 Nov;168(1):111-9. doi: 10.1016/j.imlet.2015.09.017. Epub 2015 Oct 9.

Abstract

In general, conventional chemotherapy is associated with significant toxicity leading to immunosuppression manifesting mainly in the lymphocyte depletion. This immunosuppression promotes tumor growth and elicits the tumor cell dissemination. However, chemotherapy can be immune stimulative especially in combination with an immunotherapy. In this work, we investigated in vitro effects of gemcitabine alone and in combination with interferon-alpha on splenocytes obtained from healthy and pancreatic carcinoma bearing mice. We showed that gemcitabine alone depletes the regulatory T cells in the splenocyte culture. Gemcitabine in combination with interferon-alpha demonstrated some immunomodulatory features, but these effects were interferon-alpha dependent. We concluded that combination of both drugs induces rather cumulative effects, supposing that these therapeutic could be applied together for a chemo-immunotherapy.

Keywords: Chemotherapy; Gemcitabine; Immunomodulation; Interferon-alpha; Pancreatic adenocarcinoma.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / immunology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • B7-1 Antigen / immunology
  • B7-1 Antigen / metabolism
  • B7-2 Antigen / immunology
  • B7-2 Antigen / metabolism
  • CD4-CD8 Ratio
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / immunology
  • Cells, Cultured
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / immunology
  • Flow Cytometry
  • Gemcitabine
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / immunology*
  • Mice, Inbred C57BL
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / pathology
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • B7-1 Antigen
  • B7-2 Antigen
  • Interferon-alpha
  • Deoxycytidine
  • Gemcitabine