title: Intratumoral T cell subset ratios and Fas ligand expression on brain tumor endothelium.
abstract: BACKGROUND
  T cell presence in TIL, and the ratio of CD8+ and CD4+ T cell subsets in particular, can correlate with tumor prognosis in some tumors, although the significance of such infiltration into glioma is controversial. However, gliomas represent a lower extreme in their extent of T cell infiltration, and are thus useful in assessing factors that can decrease T cell presence within tumor tissue. Fas ligand, a pro-apoptotic cell surface protein, may play a key role in reduction of T cells in tumor tissue.
  
  
  OBJECTIVE
  To assess the level of FasL expression on brain tumor endothelium and to correlate this with relative levels of CD4+ and CD8+ T cell subsets in TIL from brain tumors.
  
  
  METHODS
  CD3+, CD4+, and CD8+ cells were quantified in fresh TIL by flow cytometry. Paraffin embedded sections of tumors, including meningiomas and gliomas as well as extracranial malignancies, underwent immunohistochemical staining for FasL and Von-Willebrand's factor (Factor VIII) to determine expression levels of endothelial FasL.
  
  
  RESULTS
  FasL expression was high in aggressive intracranial malignancies compared to more indolent neoplasms, and correlated inversely with CD8+/CD4+ TIL ratios in all tumor classes combined (ANOVA, p < 0.05).
  
  
  CONCLUSIONS
  Low levels of T cells within TIL, as well as low CD8+/CD4+ TIL ratios appear to be a property of parenchymal tumor presence. Together with the inverse correlation seen between FasL expression and CD8+/CD4+ TIL ratios, the high levels of endothelial FasL expression in gliomas suggests that FasL decreases T cell presence in brain tumors in a subset-selective manner, thus contributing to glioma immune privilege.
authors.affiliation: The Marine Dunitz Neurosurgical Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Yu
authors.forename: Paul K
authors.initials: PK
authors.lastname: Lee
authors.forename: Moneeb
authors.initials: M
authors.lastname: Ehtesham
authors.forename: Ken
authors.initials: K
authors.lastname: Samoto
authors.forename: Keith L
authors.initials: KL
authors.lastname: Black
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Wheeler
mesh_terms: D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016516:CD4-CD8 Ratio; D018450:Disease Progression; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D053222:Fas Ligand Protein; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000473:pathology*
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins