Interferon gamma induction in human melanoma cell/allogeneic leukocyte co-cultures is enhanced by interleukin 18 but drug resistant melanoma cells are poorer inducers of IFN-gamma.

Abstract

Human melanoma Colo 679 cells were made resistant to doxorubicin (adriamycin, ADM) by continuous exposure to ascending concentrations of the drug and Colo/ADM80; a variant which grew continuously in the presence of 80 ng/ml of ADM was thus established. Human peripheral blood mononuclear cells (PBMC) produced interferon gamma (IFN-gamma) when cultured with mitomycin C (MMC)-treated parental Colo 679 cells. The synthesis of IFN-gamma was synergistically enhanced by adding interleukin-18 (IL-18) and this was IL-12-dependent because a neutralizing antibody against IL-12 almost completely inhibited IFN-gamma production while control antibodies (Abs) were inactive. The cellular sources of IFN-gamma were found to be B cells, CD8+ T cells and CD4+ T cells as revealed by flow cytometry after double staining for surface antigens and staining for intracellular IFN-gamma. Interestingly, the resistant cell line induced much less IFN-gamma production than the parental cell line under the same co-culture conditions; however, IL-18 could still enhance the production of IFN-gamma. In conclusion, our study shows that acquired resistance to anti-cancer agents can also reduce immune responses to cancer cells. However, the immunostimulatory cytokine IL-18 could still enhance IFN-gamma production in drug resistant tumor cell-PBMC cultures indicating that such immunostimulatory agents could still be beneficial in immunotherapy for patients with recurrent drug resistant tumors.

• Authors: M J Micallef, S Darmanin, J A Buhagiar, M T Camilleri-Podesta, H Yamauchi, M Kurimoto, A S Inglott, R Ellul-Micallef
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 1 Issue 2 Pg. 295-305 (Feb 2001) ISSN: 1567-5769 [Print] Netherlands
• PMID: 11360930 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-18
• Interleukin-12
• Doxorubicin
• Interferon-gamma

Topics

• Coculture Techniques
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm
• Flow Cytometry
• Humans
• Interferon-gamma (biosynthesis)
• Interleukin-12 (physiology)
• Interleukin-18 (pharmacology)
• Leukocytes (metabolism)
• Melanoma (drug therapy, immunology, pathology)
• Tumor Cells, Cultured