Enhancement of antitumor immunity of dendritic cells pulsed with heat-treated tumor lysate in murine pancreatic cancer

Immunol Lett. 2006 Mar 15;103(2):142-8. doi: 10.1016/j.imlet.2005.10.021. Epub 2005 Nov 15.

Abstract

Cancer vaccines using dendritic cells (DCs) have been shown to induce antitumor immunity and have recently been applied to non-immunogenic cancers, such as pancreatic cancer. In this study, we utilized DCs loaded with heat-treated tumor lysate (HTL-DC) as a vaccine in order to stimulate antitumor immunity in a murine pancreatic cancer model and compared them to DCs loaded with tumor lysate (TL-DC). The poorly immunogenic mouse ductal pancreatic cancer cell line PANC02 with syngeneic mouse strain C57BL/6 was used as a model. Inducible heat shock proteins (HSPs) were significantly increased in HTL (HSP70 and HSP90). Tumor size measurements indicated that HTL-DC induced stronger tumor suppression than unpulsed DC or TL-DC (43% reduction in tumor volume compared to control group). T cell proliferation assay and IFN-gamma ELISPOT assay showed that T cell activation increased in the following order: DC<TL-DC<HTL-DC. Furthermore, repeated HTL-DC vaccinations led to higher expansion of IFN-gamma-secreting T cells. Cytotoxicity assay revealed that HTL-DC were more efficient in priming PANC02-specific T cells. Our study identifies HTL as an effective source of tumor-associated antigens (TAAs) for pulsing DCs, and demonstrates that HTL-DC can generate a stronger and broader T cell response against fatal cancers, such as pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Dendritic Cells / immunology*
  • Female
  • Heat-Shock Proteins / physiology
  • Immunotherapy*
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / therapy
  • Spleen / cytology
  • Spleen / metabolism
  • T-Lymphocytes / physiology
  • T-Lymphocytes, Cytotoxic / physiology
  • Tissue Extracts / immunology
  • Tissue Extracts / therapeutic use*

Substances

  • Heat-Shock Proteins
  • Tissue Extracts
  • Interferon-gamma