title: Decitabine immunosensitizes human gliomas to NY-ESO-1 specific T lymphocyte targeting through the Fas/Fas ligand pathway.
abstract: BACKGROUND
  The lack of effective treatments for gliomas makes them a significant health problem and highlights the need for the development of novel and innovative treatment approaches. Immunotherapy is an appealing strategy because of the potential ability for immune cells to traffic to and destroy infiltrating tumor cells. However, the absence of well-characterized, highly immunogenic tumor-rejection antigens (TRA) in gliomas has limited the implementation of targeted immune-based therapies.
  
  
  METHODS
  We hypothesized that treatment with the demethylating agent, decitabine, would upregulate the expression of TRA on tumor cells, thereby facilitating enhanced surveillance by TRA-specific T cells.
  
  
  CONCLUSIONS
  Treatment of human glioma cells with decitabine increased the expression of NY-ESO-1 and other well characterized cancer testes antigens. The upregulation of NY-ESO-1 made these tumors susceptible to NY-ESO-1-specific T-cell recognition and lysis. Interestingly, decitabine treatment of T98 glioma cells also sensitized them to Fas-dependent apoptosis with an agonistic antibody, while a Fas blocking antibody could largely prevent the enhanced functional recognition by NY-ESO-1 specific T cells. Thus, decitabine treatment transformed a non-immunogenic glioma cell into an immunogenic target that was efficiently recognized by NY-ESO-1--specific T cells.
  
  
  CONCLUSIONS
  Such data supports the hypothesis that agents which alter epigenetic cellular processes may "immunosensitize" tumor cells to tumor-specific T cell-mediated lysis.
authors: Graduate Program in Physiological Sciences, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, 90095, USA. vkonkankit@ucla.edu
authors: Veerauo V
authors: VV
authors: Konkankit
authors: Won
authors: W
authors: Kim
authors: Richard C
authors: RC
authors: Koya
authors: Ascia
authors: A
authors: Eskin
authors: Mai-Anh
authors: MA
authors: Dam
authors: Stanley
authors: S
authors: Nelson
authors: Antoni
authors: A
authors: Ribas
authors: Linda M
authors: LM
authors: Liau
authors: Robert M
authors: RM
authors: Prins
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000601:surgery; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D000077209:Decitabine; D053222:Fas Ligand Protein / Q000378:metabolism*; D005910:Glioma / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology*; D058990:Molecular Targeted Therapy; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic; D015854:Up-Regulation / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D016207:Cytokines; C491901:FAS protein, human; D053222:Fas Ligand Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D019014:fas Receptor; D000077209:Decitabine; D001374:Azacitidine