Interleukin-28B Plays a Therapeutic Role on Mouse U14 Cervical Cancer Cells by Down-Regulating CD4+CD25+FoxP3+Regulatory T Cells In Vivo.
OBJECTIVE
To investigate the immunotherapeutic effectiveness of adenoviral vector expressing mouse interleukin (IL)-28B (Ad-mIL-28B) against cervical cancer and its mechanism.


METHODS
U14 cervical cancer cell-bearing mice were treated with Ad-mIL-28B. Meanwhile, whole cell vaccine was prepared by repeated freezing and thawing U14 cells. Then CD4⁺CD25⁺FoxP3⁺regulatory T (Treg) cells were evaluated by flow cytometry. Tumor volume and metastasis in BALB/c and C57BL/6j mice were detected.


RESULTS
Ad-mIL-28B treatment significantly decreased the number of CD4⁺CD25⁺FoxP3⁺Treg cells. Subsequently, there was a significant decrease in the size of tumor tissue and the numbers of heteromorphic tumor cells. The tumor metastasis in the lung and liver of the Ad-mIL-28B group also decreased. However, there was no therapeutic effect observed for whole cell vaccine on U14 tumor-bearing mice.


CONCLUSIONS
Interleukin-28B can inhibit the growth and metastasis of cervical cancer in U14 tumor-bearing mice by down-regulating Treg cells.
*Department of Gynecology and Obstetrics, the Second Affiliated Hospital of Lanzhou University, Lanzhou, Gansu Province, China; Institutes of †Pathogen Biology and ‡Immunology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province, China; §Institute of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province, China; and ∥Department of Obstetrics and Gynecology, Gansu Provincial Hospital, Lanzhou, Gansu Province, China.
Xiaoyun
X
Chen
Bingdong
B
Zhu
Yanping
Y
Luo
Dongdong
D
Zhang
Lang
L
Zhang
Huihui
H
Zhu
Chunyan
C
Hao
Yuzhen
Y
Guo
Huiling
H
Liu
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007124:Immunoenzyme Techniques; D007372:Interferons; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays; D000095022:Interferon Lambda
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; D007372:Interferons; D053645:Interleukin-2 Receptor alpha Subunit; D007378:Interleukins; C498833:Foxp3 protein, mouse; C000624353:interferon-lambda, human; D000095022:Interferon Lambda