Abstract
Blocking cytokine interleukin 10 (IL-10) at the time of immunisation enhances vaccine induced T cell responses and improves control of tumour cell growth in vivo. However, the effect of an IL-10 blockade on the biological function of macrophages has not been explored. In the current paper, a macrophage precursor cell line, U937 cells, was selected to investigate the differential expression of proteins and relevant cell signalling pathway changes, when stimulated with lipopolysaccharide (LPS) in the presence of antibodies to IL-10 or IL-10 receptor. We used a quantitative proteomic strategy to investigate variations in protein profiles of U937 cells following the treatments with LPS, LPS plus human anti-IL10 antibody and anti-IL10R antibody in 24hrs, respectively. The LPS treatment significantly activated actin-related cell matrix formation and immune response pathways. The addition of anti-IL10 and anti-IL10R antibody further promoted the immune response and potentially effect macrophage survival through PI3K/AKT signalling; however, the latter appeared to also upregulated oncogene XRCC5 and Cajal body associated processes.
Highlights
Cancer therapeutic vaccines are gradually becoming a cancer treatment modality, especially when combined with immune checkpoint inhibitors[1, 2]
Trifluoroacetic acid (TFA), methanol, acetonitrile (ACN), formic acid (FA), NH4HCO3, urea, dithiothreitol (DTT), iodoacetamide (IAA), sodium pyruvate, L-glutamine, G418, Blocking interleukin 10 signalling in U937 cells enhances immune response revealed by proteomic analysis lipopolysaccharide and non-essential amino acid solution were obtained from Sigma-Alderich
To reveal the molecular insights underlying the immunisation enhancement of blocking IL10, Isobaric tag for relative and absolute quantitation (iTRAQ) 4-plex labelling in conjunction with nano-LC-MS/MS was used to assess the differential expression of the proteome of U937 cells
Summary
Cancer therapeutic vaccines are gradually becoming a cancer treatment modality, especially when combined with immune checkpoint inhibitors[1, 2]. Therapeutic vaccine induced T cells, especially CD8+ T cells, are able to destroy tumour cells without damaging nearby normal cells or tissues and cause less side effects compared with conventional surgery, chemo-or radiotherapy[3, 4]. A therapeutic vaccine should elicit sufficient numbers of effector T. Blocking interleukin 10 signalling in U937 cells enhances immune response revealed by proteomic analysis. Municipal Government, award number: 2015AG1003, recipient: Xiaosong Liu. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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