Preliminary study of the inhibitory effect and mechanism of B16F10-ESAT-6-gpi/IL-21 vaccine on the pulmonary metastasis in mouse models of melanoma.
- Author:
Xiangfeng HE
1
;
Wen SHI
;
Fengshu ZHAO
;
Jianhong WANG
;
Xiaohong XU
;
Qinghe TAN
;
Yongqiang SUN
;
Dengyu CHEN
;
Jun DOU
2
Author Information
- Publication Type:Journal Article
- MeSH: Animals; CD8-Positive T-Lymphocytes; immunology; Cadherins; metabolism; Cancer Vaccines; immunology; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Female; Homeodomain Proteins; metabolism; Humans; Interferon-gamma; metabolism; Interleukins; immunology; Lung; pathology; Lung Neoplasms; metabolism; secondary; Melanoma; metabolism; pathology; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Organ Size; Transcription Factors; metabolism; Transforming Growth Factor beta2; metabolism; Zinc Finger E-box-Binding Homeobox 1
- From: Chinese Journal of Oncology 2014;36(4):245-249
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect and mechanism of B16F10-ESAT-6-gpi/IL-21 tumor cell vaccine on pulmonary metastasis in mouse model of melanoma.
METHODSTwelve 8-week old female C57BL/6 mice were used in this study. The mice were injected with wild-type B16F10 cells through tail vein after immunization with B16F10-ESAT-6-gpi/IL-21 tumor cell vaccine, and the pulmonary metastasis was observed. The CD4(+) and CD8(+) T cells were isolated by magnetic activated cell sorting, and then used for the detection of CFSE/7-AAD cytotoxicity by flow cytometry. Serum from the mice immunized with tumor-cell vaccine was used to detect IFN-γ expression by ELISA. The expression of TGF-β2, ZEB1, E-cadherin, and N-cadherin of tumor tissues was detected by RT-PCR and immunofluorescence, respectively.
RESULTSThe mice vaccinated with B16F10-ESAT-6-gpi/IL-21 had significantly fewer nodules in the lung and lower lung weight [(285.8 ± 19.01) mg vs. (406.3 ± 27.12) mg], with lower levels of TGF-β2, ZEB1 and N-cadherin proteins but higher level of E-cadherin protein within the tumor tissue, as compared with the control mice. Meanwhile, the immunized mice had significantly increased CD8(+) T cell killing activity [(42.62 ± 3.465)% vs. (22.29 ± 1.804)%] and IFN-γ expression level [(55.200 ± 7.173) pg/ml vs. (6.435 ± 1.339) pg/ml] over the control mice.
CONCLUSIONSThe B16F10-ESAT-6-gpi/IL-21 vaccine can inhibit the metastasis of melanoma in the lung in vaccinated melanoma-bearing mice. This inhibitory effect is associated with CD8(+) T cell immune response and a higher level of IFN-γ, which may influence on the mesenchymal-epithelial transition of tumor cells.