British Journal of Cancer (2011) 105, 687–693. doi:10.1038/bjc.2011.306 www.bjcancer.com
Published online 9 August 2011
Supernatants from lymphocytes stimulated with Bacillus Calmette-Guerin can modify the antigenicity of tumours and stimulate allogeneic T-cell responses
1Department of Oncology, Division of Clinical Sciences, St George's, University of London, 2nd floor, Jenner Wing, London SW17 0RE, UK
Correspondence: Dr WM Liu, E-mail: firstname.lastname@example.org
Received 6 June 2011; Revised 12 July 2011; Accepted 15 July 2011; Published online 9 August 2011.
Reduced expression of class 1 human leucocyte antigens (HLA1) is often a mechanism by which tumours evade surveillance by the host immune system. This is often associated with an immune function that is unable to mount appropriate responses against disease, which can result in a state that favours carcinogenesis.
In the current study, we have explored the effects of Bacillus Calmette-Guerin (BCG) on the cytokine output of leucocytes, which is a key determinant in generating antitumour action, and have also assessed the effect of these cytokine cocktails on HLA1 expression in solid tumour cell lines.
BCG potently activated a broad range of leucocytes, and also enhanced the production of cytokines that were Th1-predominant. Supernatants from BCG-treated leucocytes significantly increased the expression of HLA1 on the surface of cancer cell lines, which correlated with increased cytolytic T-cell activity. We also showed that the increased HLA1 expression was associated with activation of intracellular signalling pathways, which was triggered by the increases in the Th1-cytokines interferon-γ and tumour necrosis factor-α, as counteracting their effects negated the enhancement.
These studies reaffirm the role of BCG as a putative immunotherapy through their cytokine-modifying effects on leucocytes and their capacity to enhance tumour visibility.
HLA1; BCG; immunovisibility; immunotherapy; cytokines