Modulation of monocyte–tumour cell interactions by Mycobacterium vaccae
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Immunotherapy with Mycobacterium vaccae as an adjuvant to chemotherapy has recently been applied to treatment of patients with cancer. One of the mechanisms of antitumour activity of Mycobacterium bovis bacillus Calmette-Guérin (BCG), the prototype immunomodulator, is associated with activation of monocytes/macrophages. These studies were undertaken to determine how M. vaccae affects monocyte–tumour cell interactions and, in particular, whether it can prevent or reverse deactivation of monocytes that occurrs following their contact with tumour cells during coculture in vitro. Deactivation is characterised by the impaired ability of monocytes to produce tumour necrosis factor α (TNF-α), interleukin 12 (IL-12), and enhanced IL-10 secretion following their restimulation with tumour cells. To see whether deactivation of monocytes can be either prevented or reversed, three different strains of M. vaccae—B 3805, MB 3683, and SN 920—and BCG were used to stimulate monocytes before or after exposure to tumour cells. Pretreatment of monocytes with M. vaccae MB 3683, SN 920 and BCG before coculture resulted in increased TNF-α and decreased IL-10 production. All strains of M. vaccae and BCG used for treatment of deactivated monocytes enhanced depressed TNF-α secretion. Strain SN 920 and BCG increased IL-12 release but only BCG treatment inhibited an enhanced IL-10 production by deactivated monocytes. Thus, although some strains of M. vaccae may either prevent or reverse tumour-induced monocyte deactivation, none of them appears to be more effective than BCG.
KeywordsCancer cells Cytokines Deactivation Monocytes Mycobacterium vaccae
This study was supported by the National Committee for Scientific Research (grant No. 6 PO5A 096 20). We wish to thank Prof. Leon Sedlaczek (Centre for Microbiology and Virology, Polish Academy of Sciences, Łódź, Poland) for kind donation of M. vaccae strains. We also thank Ms Barbara Hajto and Mariola Ożóg for skillful technical assistance.
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