title: Autologous Tumor Cell Lysate-Loaded Dendritic Cell Vaccine Inhibited Tumor Progression in an Orthotopic Murine Model for Hepatocellular Carcinoma.
abstract: The immune status of the tumor microenvironment influences tumor progression, and hepatocellular carcinoma (HCC) with an immunosuppressive signature often is associated with a poor prognosis. This study examined the impact of a bone marrow-derived dendritic cell (DC) vaccine loaded with autologous tumor cell lysate on tumor progression and the tumor microenvironment using an orthotopic murine HCC model. An orthotopic murine HCC was established by implantation of Hepa1-6 cells in the liver. The impact of DC vaccine loaded with Hepa1-6 cell lysate on tumor progression, survival, and tumor-infiltrating lymphocytes and cytokines was examined. Treating mice with DC vaccine loaded with Hepa1-6 cell lysate inhibited the progression of murine HCC generated through orthotopic implantation of Hepa1-6 cells and resulted in a 90 % survival rate by day 60 compared with a survival rate lower than 5 % for untreated mice. This anti-tumor response was associated with inhibition of STAT3 phosphorylation within the tumor. The DC vaccine reduced accumulation of Foxp3+CD4+regulatory T cells within the tumor microenvironment and prevented TGF-β production from the tumor tissue. Tumor cell lysate-loaded DC vaccine prevented HCC progression in a clinically relevant orthotopic murine HCC model. The effect of DC vaccine on the accumulation of Foxp3+CD4+regulatory T cells within the tumor microenvironment and on the production of TGF-β suggests that tumor regression by DC vaccination may be associated with an altered immunosuppressive tumor microenvironment.
authors.affiliation: Department of Surgery, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Surgery, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Luan
authors.affiliation: Department of Surgery, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Warren
authors.affiliation: Department of Surgery, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Hena
authors.initials: H
authors.lastname: Kadri
authors.affiliation: Department of Surgery, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Department of Surgery, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Vadim
authors.initials: V
authors.lastname: Goz
authors.affiliation: Department of Surgery, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Sima
authors.initials: S
authors.lastname: Blank
authors.affiliation: Department of Pathology, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Isabel Fiel
authors.affiliation: Department of Surgery, The Icahn School of Medicine at Mount Sinai, New York, NY, USA. spiros.hiotis@mountsinai.org.
authors.forename: Spiros P
authors.initials: SP
authors.lastname: Hiotis
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016233:Immunotherapy, Active / Q000379:methods*; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D019496:Cancer Vaccines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016212:Transforming Growth Factor beta