[Inhibitory effect of 4-1BBL combined with Hsp70-tumor antigen peptides on pulmonary metastasis of melanoma in mice].
OBJECTIVE
Low level expression of some co-stimulatory molecules is an important mechanism for tumor to evade the attack of immunity system; up-regulating these molecules can enhance antitumor immune response. Mouse melanoma B16-F1 cell line is low immunogenic. This study was designed to investigate the inhibitory effect of co-stimulatory molecule 4-1BBL combined with hot shock protein 70 (Hsp70)-tumor antigen peptides on pulmonary metastasis of melanoma in mice, and to analyze the possible mechanism.


METHODS
After establishment of B16-F1 melanoma pulmonary metastasis model, the mice were divided into combination (4-1BBL plus Hsp70-B16) group, 4-1BBL group, Hsp70-B16-F1 group, empty vector group, and normal saline(NS) group, and relevantly received subcutaneous immunization of Hsp70-B16 peptides complex and simultaneous injection of plasmid p4-1BBL via the tail vein. Seventeen days after inoculation of B16 cells, the mice were killed to count pulmonary metastasis nodes under microscope, and to detect a series of immunologic parameters, liver function, and kidney function.


RESULTS
The number of pulmonary metastasis nodes was significantly smaller in combination group than in 4-1BBL group and Hsp70-B16 group (50+/-8 vs. 500+/-80 and 450+/-40, P0.01); the levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) in serum were significantly higher in combination group than in NS group (200.31+/-25.36 vs. 56.89+/-16.55, P0.05; 1 870.53+/-204.28 vs. 610.30+/-120.05, P0.01). The liver and kidney functions of mice in each group are normal.


CONCLUSIONS
4-1BBL in combination with Hsp70-B16 peptides can effectively inhibit melanoma pulmonary metastasis mainly through augmenting the function of peripheral T lymphocytes.
Qiu
Hui
H
Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
Zhang
Gui-Mei
GM
Zhang
Hui
H
Yuan
Ye
Y
Li
Dong
D
Feng
Zuo-Hua
ZH
D053330:4-1BB Ligand / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D018840:HSP70 Heat-Shock Proteins / Q000494:pharmacology*; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008099:Liver / Q000378:metabolism; D008175:Lung Neoplasms / Q000097:blood / Q000276:immunology* / Q000556:secondary; D008297:Male; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D014162:Transfection
D053330:4-1BB Ligand; D018840:HSP70 Heat-Shock Proteins; D007376:Interleukin-2; D007371:Interferon-gamma