title: Dendritic cells infected by Ad-sh-SOCS1 enhance cytokine-induced killer (CIK) cell immunotherapeutic efficacy in cervical cancer models.
abstract: Cervical cancer constitutes a major problem in women's health worldwide, but the efficacy of the standard therapy is unsatisfactory. Cytokine-induced killer (CIK) cells exhibit antitumor activity against a variety of malignancies in preclinical models and have proven safe and effective in clinical trials. However, current CIK therapy has limitations and needs to be improved to meet the clinical requirements. The aim of this study was to investigate whether suppressing the expression of cytokine signaling 1 (SOCS1) in dendritic cells (DCs) can shorten in vitro CIK culture time and improve its antitumor efficacy.
  
  
  
  DCs were pre-cultured for 3 days before infected with adenovirus-mediated-SOCS1 short hairpin RNA (Ad-sh-SOCS1) and pulsed with CTL epitope peptides E7. The DCs infected by Ad-sh-SOCS1 (gmDCs) and CIKs were then co-cultured for 5 or 9 days, and CIK proliferation and antitumor activity were evaluated both in vitro and in vivo.
  
  
  
  Our data show that gmDCs significantly stimulated the expansion of co-cultured CIKs and increased the secretion of interferon-γ and interleukin-12. Moreover, gmDCs-activated CIKs showed higher cytotoxic activity against TC-1 cells expressing HPV16E6 and E7. Our in vivo study showed that the mice infused with gmDCs-activated CIKs on day 10 had an increased survival rate and prolonged survival time compared with the controls.
  
  
  
  Taken together, these results indicate that DCs modified by adenovirus-mediated SOCS1 silencing can promote CIKs expansion and enhance the efficacy of antitumor immunotherapy both in vitro and in vivo, which represents an effective therapeutic approach for cervical cancer and other tumors.
authors.affiliation: The Central Laboratory, Guangming New District People's Hospital, Shenzhen, China; School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Institute of Virology, School of Medicine, State Key Laboratory of Virology, Wuhan University, Wuhan, China.
authors.forename: Bicheng
authors.initials: B
authors.lastname: Hu
authors.affiliation: School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, China.
authors.forename: Shenggao
authors.initials: S
authors.lastname: Xie
authors.affiliation: School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, China.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, China.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, College of Life Sciences, Hubei University, Wuhan, China.
authors.forename: Wanping
authors.initials: W
authors.lastname: Chen
authors.affiliation: Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, College of Life Sciences, Hubei University, Wuhan, China. Electronic address: shl@hubu.edu.cn.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address: hubo96073@hotmail.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D055612:Cytokine-Induced Killer Cells / Q000166:cytology* / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D018664:Interleukin-12 / Q000097:blood / Q000378:metabolism; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering / Q000378:metabolism*; D013194:Staining and Labeling; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000378:metabolism*; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy*
chemical_list: D015415:Biomarkers; D034741:RNA, Small Interfering; D000071222:Suppressor of Cytokine Signaling 1 Protein; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: cervical cancer; cytokine-induced killer cells; dendritic cells; human papillomavirus; suppressors of cytokine signaling 1