Intratumoral injection of interferon-gamma gene-modified dendritic cells elicits potent antitumor effects: effective induction of tumor-specific CD8+ CTL response.
To examine the antitumor efficacy of intratumoral injection of interferon-gamma gene-modified dendritic cells (DC-IFN-gamma) in a B16 melanoma model and to investigate its related immunological mechanisms.



C57BL/6 mice-derived DC were transfected with adenovirus encoding IFN-gamma or beta-galactosidase (DC-LacZ). Secretion of IFN-gamma and TNF-alpha by DC was detected by ELISA. Nitric oxide (NO) production was measured by Griess reaction. Cytotoxicity of DC against tumor cell lines and activity of cytotoxic T lymphocytes (CTLs) were determined by 51Cr-release assay. TRP-2aa180-188-specific CD8+ CTLs in tumor-bearing mice with different treatment were determined by ELISPOT.



DC-IFN-gamma could secrete high levels of IFN-gamma, NO and TNF-alpha. DC-IFN-gamma were cytolytic to B16 melanoma cells in vitro, but DC-LacZ and DC were not. Significant inhibition of tumor growth and prolonged survival were achieved in tumor-bearing mice intratumorally injected with DC-IFN-gamma when compared with those in tumor-bearing mice intratumorally injected with DC, DC-LacZ, fibroblasts, IFN-gamma gene-modified fibroblasts or PBS. After treatment with DC-IFN-gamma, enhanced Th1 and decreased Th2 responses were observed, and B16 melanoma antigen TRP-2aa180-188-specific CD8+ CTLs were induced significantly in the tumor-bearing mice.



Intratumorally injected DC-IFN-gamma can uptake tumor antigens in situ and cross-present tumor antigens to specific CD8+ T cells, hereby eliciting effective antitumor effects in murine model with preestablished B16 melanoma.
Pan
Jianping
J
Institute of Immunology, Zhejiang University, 353 Yan'an Road, 310031, Hangzhou , P.R. China.
Zhang
Minghui
M
Wang
Jianli
J
Wang
Qingqing
Q
Xia
Dajing
D
Sun
Wenji
W
Zhang
Lihuang
L
Yu
Hai
H
Cao
Xuetao
X
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002857:Chromium / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015552:Injections, Intralesional; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D002857:Chromium; D009569:Nitric Oxide; D007371:Interferon-gamma; D001616:beta-Galactosidase