IL-10 signalling blockade at the time of immunization inhibits Human papillomavirus 16 E7 transformed TC-1 tumour cells growth in mice

Cell Immunol. 2014 Jul;290(1):145-51. doi: 10.1016/j.cellimm.2014.06.002. Epub 2014 Jun 18.

Abstract

IL-10 signalling blockade by intra-peritoneal injection of anti-IL-10 receptor antibodies at the time of immunization enhances vaccine induced CD8+ T cell responses and promotes bacteria, parasitic and viral control. We now show that blockade of IL-10 signalling at the time of immunization enhances vaccine induced antigen specific CD8+ T cell responses to both dominant and subdominant CTL epitopes. Injection of anti-IL-10 receptor antibodies subcutaneous at the time of immunization also enhances CD8+ T cell responses. Furthermore, IL-10 signalling blockade at the time of a Human papillomavirus 16 E7 peptide/LPS immunization, prevents HPV16 E7 transformed TC-1 tumour growth in mice. Immunization in the presence of anti-IL-10R antibodies and Monophosphoryl lipid A, generates antigen specific CD8+ T cell responses similar to immunization with LPS. Our results suggest that immunization and IL-10 signalling blockade may provide a novel way for the development of therapeutic vaccines against cancer.

Keywords: Cervical cancer; IL10; Immunotherapy.

MeSH terms

  • Animals
  • Antibodies / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line, Transformed
  • Cell Proliferation
  • Female
  • Human papillomavirus 16 / genetics
  • Humans
  • Immunization
  • Interleukin-10 / antagonists & inhibitors*
  • Interleukin-10 / immunology
  • Lipid A / analogs & derivatives
  • Lipid A / pharmacology
  • Lipopolysaccharides / immunology
  • Mice
  • Mice, Inbred C57BL
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus E7 Proteins / immunology*
  • Papillomavirus Vaccines / immunology*
  • Receptors, Interleukin-10 / immunology
  • Signal Transduction / immunology
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / prevention & control
  • Uterine Cervical Neoplasms / therapy

Substances

  • Antibodies
  • IL10 protein, mouse
  • Lipid A
  • Lipopolysaccharides
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines
  • Receptors, Interleukin-10
  • oncogene protein E7, Human papillomavirus type 16
  • Interleukin-10
  • monophosphoryl lipid A