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

 Han-Soo Kim  ;  Yee Shin Choo  ;  Taeseok Koo  ;  Seungmin Bang  ;  Tae Yun Oh  ;  Jing Wen  ;  Si Young Song 
 IMMUNOLOGY LETTERS, Vol.103(2) : 142-148, 2006 
Journal Title
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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*
Dendritic cells ; Immunotherapy ; Tumor lysate ; Murine pancreatic cancer
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-γ 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-γ-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.
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1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Han Soo(김한수)
Bang, Seungmin(방승민) ORCID logo https://orcid.org/0000-0001-5209-8351
Song, Si Young(송시영) ORCID logo https://orcid.org/0000-0002-1417-4314
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