The Therapeutic Role of NK Cells in DC Immunotherapy

Natural-Killer-Cell;Dendritic-Cell-Immunotherapy;Melanoma;Streptococcus-salivarius-K12;Murine;Interferon-gamma;Perforin

Caldwell, Felicity Jane ; McLellan, Alexander

University of Otago

关键词: Natural-Killer-Cell;    Dendritic-Cell-Immunotherapy;    Melanoma;    Streptococcus-salivarius-K12;    Murine;    Interferon-gamma;    Perforin;   

Others  :  https://ourarchive.otago.ac.nz/bitstream/10523/4486/1/CaldwellFelicityJ2013BiomedScHons.pdf

美国|英语

来源: Otago University Research Archive

【 摘 要 】

Dendritic cell (DC) immunotherapy is a promising treatment for cancer. Despite now being used in the clinic, the role and mechanisms of lymphocyte subsets stimulated by DC immunotherapy are not completely understood. Potential mechanisms for anti-tumour responses include cytokine (e.g. interferon-gamma; IFN-γ) or direct cell-killing mechanisms (e.g. perforin) performed by natural killer (NK) cells, NKT cells or CD4+ and CD8+ T cells. This current study used a B16/OVA-melanoma tumour model with bacteria-stimulated dendritic cells, coupled with antibody-mediated depletions (NK cells, CD4+ and CD8+ T cells and IFN-γ) and mice genetically deficient in IFN-γ and perforin to determine the mechanism of successful DC immunotherapy. In agreement with previous work, CD4+ T cell, CD8+ T cell and NK cell depletion resulted in a loss in efficacy of DC immunotherapy, although in this study, this effect failed to reach statistical significance for all lymphocytes. We found that DC immunotherapy induced an IFN-γ, not perforin, mediated anti-tumour response against B16/OVA melanoma tumour. Determining the role and mechanism of killing tumour cells in DC immunotherapy is of great importance and could lead to improvements in DC immunotherapy strategies. Showing particular promise is optimisation of IFN-γ release to enhance a potent anti-tumour response.