Original Article

Cancer Immunology, Immunotherapy

, Volume 56, Issue 11, pp 1831-1843

Dendritic cells modified with 6Ckine/IFNγ fusion gene induce specific cytotoxic T lymphocytes in vitro

  • Gang XueAffiliated withDepartment of General Surgery, Chengdu Army General Hospital
  • , Ran-yi LiuAffiliated withState Key Laboratory of Oncology in South China, Room 619, Cancer Center, Sun Yat-sen University
  • , Yan LiAffiliated withState Key Laboratory of Oncology in South China, Room 619, Cancer Center, Sun Yat-sen University
  • , Ying ChengAffiliated withDepartment of Endocrinology, Chengdu Army General Hospital
  • , Zhi-hui LiangAffiliated withState Key Laboratory of Oncology in South China, Room 619, Cancer Center, Sun Yat-sen University
  • , Jiang-xue WuAffiliated withState Key Laboratory of Oncology in South China, Room 619, Cancer Center, Sun Yat-sen University
  • , Mu-sheng ZengAffiliated withState Key Laboratory of Oncology in South China, Room 619, Cancer Center, Sun Yat-sen University
  • , Fu-zhou TianAffiliated withDepartment of General Surgery, Chengdu Army General Hospital
  • , Wenlin HuangAffiliated withState Key Laboratory of Oncology in South China, Room 619, Cancer Center, Sun Yat-sen UniversityBeijing Institute of Microbiology, Chinese Academy of Sciences Email author 

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Abstract

Backgroud and objective

Dendritic cells play an important role in initiation and regulation of immune responses. Previous studies demonstrated that intratumoral administration of 6Ckine-modified DCs enhanced local and systemic antitumor effects. Herein we report the investigation of the specific CTL responses elicited by adenoviral 6Ckine/IFNγ fusion gene-modified DCs in vitro.

Methods

Human monocyte-derived DCs were modified with an adenoviral vector encoding 6Ckine/IFNγ fusion protein (Ad-6Ckine/IFNγ), and then investigated the effect of 6Ckine/IFNγ fusion protein on the maturation, cytokine and chemokine secretion of DCs, and their activities of recruiting and activating T cells in vitro were investigated.

Results

6Ckine/IFNγ fusion protein induced DC maturation characterized with the upregulation of CD83 and CCR7. And it up-regulated the expression of RANTES and IL-12p70, down-regulated that of IL-10 in DCs. Additionally, 6Ckine/IFNγ markedly increased DC’s recruiting ability for naive T cells, benefiting from the enhanced expression of chemokines 6Ckine and RANTES in DCs. Fusion gene-modified DCs significantly promoted the proliferation of autologous T cells, induced Th1 differentiation by upregulating the expression of IL-2 and T-bet in T cells, and increased specific cytotoxicity of CTLs against specific tumor cells, HepG2 or LoVo cells, respectively.

Conclusion

Combining the effects of 6Ckine and IFNγ, Ad-6Ckine/IFNγ modified DCs induced enhanced CTL responses in vitro, which indicated that Ad-6Ckine/IFNγ modified DCs might be used as an adjuvant to trigger an effective antitumor immune response.

Keywords

Dendritic cells Cytokines Chemokines Tumor immunology Gene therapy