title: Human glioma immunobiology in vitro: implications for immunogene therapy.
abstract: OBJECTIVE
  Human gliomas are known to be immunosuppressive. Recent reports have suggested novel strategies to overcome this immunosuppression, including immunogene therapy. We examined expression of 10 immunologically important molecules by human gliomas in vitro, and we discuss the implications for immunogene therapy.
  
  
  METHODS
  Early passage human glioma cultures and established human glioma cell lines were analyzed by flow cytometry for expression of Class I and II major histocompatibility complex (MHC), B7-2 (CD86), and Fas (CD95). Culture supernatants were assayed by enzyme-linked immunosorbent assay for interleukin (IL)-6, IL-10, IL-12, transforming growth factor beta2, prostaglandin E2, and granulocyte-macrophage colony-stimulating factor levels.
  
  
  RESULTS
  All cultures (16 of 16 samples) expressed Class I MHC and Fas, but few expressed Class II MHC (1 of 16 samples) or B7-2 (0 of 16 samples). Nearly all expressed high levels of IL-6 (19 of 21 samples; mean, 36.5 +/- 10.8 ng/10(6) cells/d) and prostaglandin E2 (21 of 21 samples; mean, 15.6 +/- 4.5 ng/10(6) cells/d) levels, and many expressed transforming growth factor beta2 (13 of 21 samples; mean, 8.6 +/- 3.7 ng/10(6) cells/d). Although several cultures (6 of 14 samples) expressed granulocyte-macrophage colony-stimulating factor, expression levels were very low (mean, 0.2 +/- 0.1 ng/10(6) cells/d). Few cultures (4 of 21 samples) expressed measurable IL-10, and none (0 of 22 samples) expressed IL-12.
  
  
  CONCLUSIONS
  Class I MHC and Fas expression suggests that human glioma cells may be susceptible to Class I MHC-dependent cytotoxic T cell recognition and Fas-mediated killing. Unfortunately, transforming growth factor beta2 and prostaglandin E2 probably impair T cell activation, and IL-6 may shift immunity to less effective humoral (T helper 2) responses. Proinflammatory gene expression (B7-2, granulocyte-macrophage colony-stimulating factor, and/or IL-12) is lacking. Together, these results suggest that modifying glioma cells via proinflammatory gene transfer or immunoinhibitory gene suppression might stimulate immune responses that are effective against unmodified tumors.
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Canada.
authors.forename: I F
authors.initials: IF
authors.lastname: Parney
authors.forename: M A
authors.initials: MA
authors.lastname: Farr-Jones
authors.forename: L J
authors.initials: LJ
authors.lastname: Chang
authors.forename: K C
authors.initials: KC
authors.lastname: Petruk
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics; D051940:B7-2 Antigen; D001932:Brain Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D018014:Gene Transfer Techniques; D005805:Genes, MHC Class I / Q000235:genetics; D005802:Genes, MHC Class II / Q000235:genetics*; D015316:Genetic Therapy; D005910:Glioma / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology; D066298:In Vitro Techniques; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000235:genetics
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; D008562:Membrane Glycoproteins; D019014:fas Receptor