title: Antigen-specific T cell response from dendritic cell vaccination using side population cell-associated antigens targets hepatocellular carcinoma.
abstract: Dendritic cell (DC) vaccination targeting cancer stem cells is an effective way to suppress tumor progression and reduce the metastasis and recurrence. In the present study, we explored the suitability of side population (SP) cells as source of antigens for DC vaccination against hepatocellular carcinoma (HCC) in a mouse model. In this study, we identified the "stem-like" characteristics of SP cells in the MHCC97 and Hepa 1-6 HCC cell lines. We found that SP cells express high levels of tumor-associated antigens and MHC class I molecules. Although loading with cell lysates did not change the characteristics of DCs, SP cell lysate-pulsed DCs induced antigen-specific T cell responses, including T cell proliferation and increased IFN-γ production by stimulated CD8(+) T cells. We investigated the cytotoxicity of T cells stimulated by SP cell lysate-pulsed DCs in nude mice co-injected with MHCC97 cells. To mimic the in vivo environment, we also confirmed the result in mouse HCC cell line Hepa 1-6 induced tumor-bearing C57/BL6 immune competent mice, and we demonstrated that vaccination with DCs loaded with Hepa 1-6 SP cell lysates could induce a T cell response in vivo and suppress the tumor growth. Our results may have applications for anti-HCC immunotherapy by targeting the cancer stem cells and may provide new insight for cancer vaccines.
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaan xi, 710032, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaan xi, 710032, People's Republic of China.
authors.forename: Zhuochao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: The Second Department of General Surgery, The First Hospital of Qiqihaer City, Qiqihaer, Heilongjiang, 161005, People's Republic of China.
authors.forename: Guoying
authors.initials: G
authors.lastname: Lin
authors.affiliation: The Second Department of General Surgery, The First Hospital of Qiqihaer City, Qiqihaer, Heilongjiang, 161005, People's Republic of China.
authors.forename: Yuanxing
authors.initials: Y
authors.lastname: Gao
authors.affiliation: The Second Department of General Surgery, The First Hospital of Qiqihaer City, Qiqihaer, Heilongjiang, 161005, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
authors.affiliation: The Second Department of General Surgery, The First Hospital of Qiqihaer City, Qiqihaer, Heilongjiang, 161005, People's Republic of China.
authors.forename: Heliang
authors.initials: H
authors.lastname: Yin
authors.affiliation: The Second Department of General Surgery, The First Hospital of Qiqihaer City, Qiqihaer, Heilongjiang, 161005, People's Republic of China.
authors.forename: Bingyi
authors.initials: B
authors.lastname: Sun
authors.affiliation: The Second Department of General Surgery, The First Hospital of Qiqihaer City, Qiqihaer, Heilongjiang, 161005, People's Republic of China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Wang
authors.affiliation: The Second Department of General Surgery, The First Hospital of Qiqihaer City, Qiqihaer, Heilongjiang, 161005, People's Republic of China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Integrative Research Center, The First Hospital of Qiqihaer City, Qiqihaer, Heilongjiang, 161005, People's Republic of China. chenhong618@tom.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: The Second Department of General Surgery, The First Hospital of Qiqihaer City, Qiqihaer, Heilongjiang, 161005, People's Republic of China. caodayong678@sina.com.
authors.forename: Dayong
authors.identifier: http://orcid.org/0000-0002-9518-1646
authors.initials: D
authors.lastname: Cao
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008113:Liver Neoplasms / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000276:immunology; D016133:Polymerase Chain Reaction; D058985:Side-Population Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D023041:Xenograft Model Antitumor Assays
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines
keywords: Cancer stem cells; Cytotoxic T lymphocytes; Dendritic cells; Hepatocellular carcinoma; Side population cells