title: Class II transactivator-induced MHC class II expression in pancreatic cancer cells leads to tumor rejection and a specific antitumor memory response.
abstract: OBJECTIVE
  The loss of major histocompatibility complex (MHC) classes I and II is a well-known mechanism by which cancer cells are able to escape from immune recognition. In this study, we analyzed the expression of antigen processing and presenting molecules in 2 cell lines derived from mouse models of pancreatic ductal adenocarcinoma (PDA) and the effects of the re-expression of MHC class II on PDA rejection.
  
  
  METHODS
  The PDA cell lines were analyzed for the expression of MHC class I, II, and antigen-processing molecules by flow cytometry or polymerase chain reaction. We generated stable PDA-MHC class II transactivator (CIITA) cells and injected them into syngeneic mice. The CD4 and CD8 T-cell role was analyzed in vitro and in vivo.
  
  
  RESULTS
  Murine PDA cell lines were negative for MHC and antigen-processing molecules, but their expression was restored by exogenous interferon-γ. CIITA-tumor cells were rejected in 80% to 100% of injected mice, which also developed long-lasting immune memory. In vitro assays and immunohistochemical analyses revealed the recruitment of T effector cells and CD8 T cells into the tumor area.
  
  
  CONCLUSIONS
  Overall, these data confirm that immunotherapy is a feasible therapeutic approach to recognize and target an aggressive cancer such as PDA.
authors.affiliation: From the *Center for Experimental Research and Medical Studies, Città della Salute e della Scienza di Torino; and †Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino; ‡Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy; §UGC Laboratorio Clinico, Hospital Universitario Virgen de las Nieves; and ∥Department of Bioquımica, Biologia Molecular e Inmunologia III, Universidad de Granada, Granada, Spain.
authors.forename: Chaitanya Ramesh
authors.initials: CR
authors.lastname: Ekkirala
authors.forename: Paola
authors.initials: P
authors.lastname: Cappello
authors.forename: Roberto S
authors.initials: RS
authors.lastname: Accolla
authors.forename: Mirella
authors.initials: M
authors.lastname: Giovarelli
authors.forename: Irene
authors.initials: I
authors.lastname: Romero
authors.forename: Cristina
authors.initials: C
authors.lastname: Garrido
authors.forename: Angel Miguel
authors.initials: AM
authors.lastname: Garcia-Lora
authors.forename: Francesco
authors.initials: F
authors.lastname: Novelli
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006084:Graft Rejection; D006183:H-2 Antigens / Q000096:biosynthesis; D064532:Histocompatibility Antigen H-2D / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D007156:Immunologic Memory; D007167:Immunotherapy; D007371:Interferon-gamma / Q000494:pharmacology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014162:Transfection
chemical_list: D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D007371:Interferon-gamma