title: Tumor-derived exosomes elicit tumor suppression in murine hepatocellular carcinoma models and humans in vitro.
abstract: Hepatocellular carcinoma (HCC) remains a global challenge due to high morbidity and mortality rates and poor response to treatment. Immunotherapy, based on introduction of dendritic cells (DCs) activated by tumor cell lysates as antigens ex vivo, shows limited response rates in HCC patients. Here, we demonstrate that tumor cell-derived exosomes (TEXs), displaying an array of HCC antigens, can elicit a stronger immune response than cell lysates in vitro and in vivo. Significant tumor growth inhibition was achieved in ectopic and orthotopic HCC mice treated with TEX-pulsed DCs. Importantly, the tumor immune microenvironment was significantly improved in orthotopic HCC mice treated by TEX-pulsed DCs, demonstrated by increased numbers of T lymphocytes, elevated levels of interferon-γ, and decreased levels of interleukin-10 and tumor growth factor-β in tumor sites. As expected, T cells played an essential role in the TEX-pulsed DC-mediated immune response. Notably, exosomes from HCC cells not only promoted HCC-specific cytolysis but also provided cross-protective effects against pancreatic cancer cells. Moreover, HCC-specific cytolysis, elicited by DCs pulsed with human HepG2 cell-derived exosomes, was observed across different human HCC cells irrespective of human leukocyte antigen types.
  
  
  
  HCC TEXs can potently carry HCC antigens, trigger a strong DC-mediated immune response, and improve the HCC tumor microenvironment. (Hepatology 2016;64:456-472).
authors.affiliation: Department of Cell Biology and Research Centre of Basic Medical Science, Tianjin Medical University, Heping District, Tianjin, China.|Third Central Clinical College, Tianjin Medical University, Hedong District, Tianjin, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Rao
authors.affiliation: Department of Cell Biology and Research Centre of Basic Medical Science, Tianjin Medical University, Heping District, Tianjin, China.
authors.forename: Bingfeng
authors.initials: B
authors.lastname: Zuo
authors.affiliation: Department of Cell Biology and Research Centre of Basic Medical Science, Tianjin Medical University, Heping District, Tianjin, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Cell Biology and Research Centre of Basic Medical Science, Tianjin Medical University, Heping District, Tianjin, China.
authors.forename: Xianjun
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Cell Biology and Research Centre of Basic Medical Science, Tianjin Medical University, Heping District, Tianjin, China.|Tianjin Cancer Hospital, Tianjin Medical University, Hexi District, Tianjin, China.
authors.forename: Abin
authors.initials: A
authors.lastname: You
authors.affiliation: Third Central Clinical College, Tianjin Medical University, Hedong District, Tianjin, China.
authors.forename: Chenxuan
authors.initials: C
authors.lastname: Wu
authors.affiliation: Third Central Clinical College, Tianjin Medical University, Hedong District, Tianjin, China.|Department of Hepatobiliary Surgery, Key Laboratory of Artificial Cell, Institute for Hepatobiliary Diseases, Third Central Hospital, Tianjin Medical University, Hedong District, Tianjin, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Du
authors.affiliation: Department of Cell Biology and Research Centre of Basic Medical Science, Tianjin Medical University, Heping District, Tianjin, China.
authors.forename: HaiFang
authors.initials: H
authors.lastname: Yin
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy*; D002460:Cell Line; D055354:Exosomes; D005240:Feasibility Studies; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D018832:Molecular Chaperones; D013601:T-Lymphocytes; D059016:Tumor Microenvironment
chemical_list: D018832:Molecular Chaperones