title: Immunotherapy of hepatocellular carcinoma: is there a place for regulatory T-lymphocyte depletion?
abstract: Immunotherapy represents a potential therapeutic option for patients with hepatocellular carcinoma (HCC), especially as secondary treatment to prevent recurrence. It has been shown that a patient's survival is directly correlated to the type and number of tumor-infiltrating immune cells, indicating that immune responses have a direct effect on the clinical course of the disease. We have assessed the potential of immunotherapy against HCC in preclinical models of low tumor burden. An antigen-specific strategy targeting α-fetoprotein, and consisting of immunization with a DNA-based synthetic vector (DNAmAFP/704), was tested on an autochthonous model of chemical hepatocarcinogenesis and led to an important (65%) reduction of the tumor burden. A nonspecific approach of CD25(+) T-cell depletion by injection of PC61 antibody was also tested on an orthotopic HCC model and led to a significant protection against tumor development. Antigen-specific immunotherapy and Treg depletion are promising strategies in physiologically relevant HCC preclinical models. Future clinical trials will demonstrate if a combination of Treg depletion with an antigen-specific immunotherapy will also translate into clinical responses in HCC patients.
authors.affiliation: INSERM U948, Biothérapies Hépatiques, CHU Hotel Dieu, Nantes, France.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Cany
authors.forename: Lucile
authors.initials: L
authors.lastname: Tran
authors.forename: Vanessa
authors.initials: V
authors.lastname: Gauttier
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Judor
authors.forename: Georges
authors.initials: G
authors.lastname: Vassaux
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ferry
authors.forename: Sophie
authors.initials: S
authors.lastname: Conchon
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D004052:Diethylnitrosamine / Q000008:administration & dosage; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D016219:Immunotherapy, Adoptive; D008113:Liver Neoplasms / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008212:Lymphocyte Depletion; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D004052:Diethylnitrosamine