Enhancement of antitumor immunity of dendritic cells pulsed with heat-treated tumor lysate in 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-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.
Kim
Han-Soo
HS
Brain Korea 21 Project of Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
Choo
Yee Shin
YS
Koo
Taeseok
T
Bang
Seungmin
S
Oh
Tae Yun
TY
Wen
Jing
J
Song
Si Young
SY
D000818:Animals; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006360:Heat-Shock Proteins / Q000502:physiology; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000628:therapy; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D014020:Tissue Extracts / Q000276:immunology / Q000627:therapeutic use*
D006360:Heat-Shock Proteins; D014020:Tissue Extracts; D007371:Interferon-gamma