Heat-shocked tumor cell lysate-pulsed dendritic cells induce effective anti-tumor immune response in vivo.
OBJECTIVE
To study whether heat-shocked tumor cells could enhance the effect of tumor cell lysate-pulsed dendritic cells (DCs) in evoking anti-tumor immune response in vivo.


METHODS
Mouse undifferentiated colon cancer cells (CT-26) were heated at 42 degrees Celsius for 1 h and then frozen-thawed. The bone marrow-derived DCs pulsed with heat-shocked CT-26 cell lysate (HSCT-26 DCs) were recruited to immunize syngeneic naive BALB/c mice. The cytotoxic activity of tumor specific cytotoxic T lymphocytes (CTLs) in mouse spleen was evaluated by IFN-enzyme-linked immunospot (ELISpot) and LDH release assay. The immunoprophylactic effects induced by HSCT-26 DCs in mouse colon cancer model were compared to those induced by single CT-26 cell lysate-pulsed DCs (CT-26 DCs) on tumor volume, peritoneal metastasis and survival time of the mice.


RESULTS
Heat-treated CT-26 cells showed a higher hsp70 protein expression. Heat-shocked CT-26 cell lysate pulsing elevated the co-stimulatory and MHC-II molecule expression of bone marrow-derived DCs as well as interleukin-12 p70 secretion. The IFN-gamma secreting CTLs induced by HSCT-26 DCs were significantly more than those induced by CT-26 DCs (P=0.002). The former CTLs' specific cytotoxic activity was higher than the latter CTLs' at a serial E/T ratio of 10:1, 20:1, and 40:1. Mouse colon cancer model showed that the tumor volume of HSCT-26 DC vaccination group was smaller than that of CT-26 DC vaccination group on tumor volume though there was no statistical difference between them (24 mm3 vs 8 mm3, P=0.480). The median survival time of mice immunized with HSCT-26 DCs was longer than that of those immunized with CT-26 DCs (57 d vs 43 d, P=0.0384).


CONCLUSIONS
Heat-shocked tumor cell lysate-pulsed DCs can evoke anti-tumor immune response in vivo effectively and serve as a novel DC-based tumor vaccine.
Department of General Surgery, The Second Hospital of Xioan Jiaotong University, Xioan 710004, Shaanxi Province, China. qiujian263@126.com
Jian
J
Qiu
Guo-Wei
GW
Li
Yan-Fang
YF
Sui
Hong-Ping
HP
Song
Shao-Yan
SY
Si
Wei
W
Ge
D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002457:Cell Extracts / Q000276:immunology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006358:Hot Temperature; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D015996:Survival Rate
D000970:Antineoplastic Agents; D002457:Cell Extracts; D016207:Cytokines