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Title: | 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 |
Authors: | Micallef, Mark J. Darmanin, Stephanie Buhagiar, Joseph A. Camilleri-Podesta, Marie Therese Yamauchi, Hiroshi Kurimoto, Masashi Serracino-Inglott, Anthony Ellul-Micallef, Roger |
Keywords: | Melanoma -- Pathophysiology Melanoma -- Diagnosis Melanoma -- Treatment Cell interaction Drug resistance in cancer cells Immunosuppression Doxorubicin |
Issue Date: | 2001 |
Publisher: | Elsevier |
Citation: | Micallef, M. J., Darmanin, S., Buhagiar, J. A., Camilleri-Podesta, M. T., Yamauchi, H., Kurimoto, M., ... & Ellul-Micallef, R. (2001). 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-γ. International Immunopharmacology, 1(2), 295-305. |
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. |
URI: | https://www.um.edu.mt/library/oar/handle/123456789/55101 |
Appears in Collections: | Scholarly Works - FacM&SPha Scholarly Works - FacSciBio |
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