title: Therapeutic antitumor efficacy of tumor-derived autophagosome (DRibble) vaccine on head and neck cancer.
abstract: OBJECTIVE
  Vaccines play important roles in antitumor biotherapy. Autophagy in tumor cells plays a critical role in depredating proteins, including tumor-specific antigens and tumor-associated antigens. We aimed to induce and collect tumor-derived autophagosomes (DRibbles) from tumor cells as a novel antitumor vaccine by inhibiting the functions of proteasomes and lysosomes.
  
  
  METHODS
  DRibbles were prepared and their morphological and autophagic properties characterized. Dendritic cells (DCs) generated from the bone marrow monocytes of mice were cocultured with DRibbles, then surface molecules of DCs and B cells, as well as apoptosis of DCs, were determined by flow cytometry. Meanwhile, functional properties of the DRibble-DCs were examined by mixed lymphocyte reactions and animal experiments.
  
  
  RESULTS
  The diameter of autophagic nanoparticles with spherical and double-membrane structure was between 200 nm and 500 nm. DRibbles resulted in the upregulation of costimulatory molecules CD40 and CD86 as well as major histocompatibility complex (MHC)-I molecules on DCs, but not MHC-II. The expressions of CD40, CD80, and CD86 and that of MHC-II molecules on B cells were also upregulated. Moreover, suppression of tumor growth and lifetime prolongation was observed in DRibble-DC-vaccinated tumor-bearing mice.
  
  
  CONCLUSIONS
  Our results demonstrate that naïve T cells can be activated effectively by DC cross-presenting antigens on upregulated MHC-I, suggesting that DRibbles be deployed as an effective antitumor vaccine for head and neck cancer immunotherapy in clinical trials.
authors: Center Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, Nanjing University, Nanjing, People's Republic of China.
authors: Hang
authors: H
authors: Su
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, People's Republic of China.
authors: Qiong
authors: Q
authors: Luo
authors: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, People's Republic of China.
authors: Hao
authors: H
authors: Xie
authors: Center Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, Nanjing University, Nanjing, People's Republic of China.
authors: Xiaofeng
authors: X
authors: Huang
authors: Center Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, Nanjing University, Nanjing, People's Republic of China.
authors: Yanhong
authors: Y
authors: Ni
authors: Center Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, Nanjing University, Nanjing, People's Republic of China.
authors: Yongbin
authors: Y
authors: Mou
authors: Center Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, Nanjing University, Nanjing, People's Republic of China ; Leeds Dental Institute, Faculty of Medicine and Health, University of Leeds, Leeds, UK.
authors: Qingang
authors: Q
authors: Hu
mesh_terms: D000818:Animals; D001343:Autophagy / Q000276:immunology*; D019496:Cancer Vaccines; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000517:prevention & control; D051379:Mice
chemical_list: D019496:Cancer Vaccines
keywords: antitumor immunity; autophagy; dendritic cells; head and neck cancer; nanoparticles