Cancer Management and Research (Mar 2018)

Immunocompetence and mechanism of the DRibble-DCs vaccine for oral squamous cell carcinoma

  • Dong H,
  • Su H,
  • Chen L,
  • Liu K,
  • Hu HM,
  • Yang WD,
  • Mou YB

Journal volume & issue
Vol. Volume 10
pp. 493 – 501

Abstract

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Heng Dong,1,2,* Hang Su,3,* Lin Chen,1 Kai Liu,1 Hong-ming Hu,2 Weidong Yang,1 Yongbin Mou1,2 1Central Laboratory, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China; 2Laboratory of Cancer Immunobiology, Robert W Franz Cancer Research Center, Earle A Chiles Research Institute, Providence Cancer Center, Portland, OR, USA; 3Department of Implantology, The Affiliated Stomatology Hospital of Tongji University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Due to the high-quality immunogenicity of tumor-derived autophagosomes (DRibbles), we aimed to explore the antitumor ability and mechanism of DRibble-loaded dendritic cells (DRibble-DCs).Materials and methods: DRibbles extracted from the oral squamous cell carcinoma cell line SCC7 express specific LC3-II and ubiquitination marker. Immunization of mice with the DRibble-DCs vaccine led to the proliferation and differentiation of CD3+CD4+IFN-γ+ and CD3+CD8+IFN-γ+ T cells. The expression of proteins in endoplasmic reticulum stress (ERS) pathways was determined by Western blotting. Additionally, the functional properties of the DRibble-DCs were examined in mice, and regulatory T cells were measured by flow cytometry.Results: Excellent biocompatibility was observed in vitro when DCs were loaded with DRibbles. T cells of lymph nodes and spleens from mice immunized with DRibble-DCs had cytotoxic effects on SCC7 cells. DCs homeostasis and ERS-related proteins were affected by DRibbles. Moreover, the DRibble-DCs vaccine achieved significantly better antitumor efficacy than DRibbles and tumor cell lysate-loaded DCs.Conclusion: The results validated the antitumor immune responses to the DRibble-DCs vaccine in vivo and in vitro. The ERS pathway can be affected by DRibbles. Keywords: dendritic cells, DRibbles, oral squamous cell carcinoma, endoplasmic reticulum stress, antigen cross-presentation, vaccine, autophagosome

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