Intratumoral T cell subset ratios and Fas ligand expression on brain tumor endothelium

J Neurooncol. 2003 Aug-Sep;64(1-2):55-61. doi: 10.1007/BF02700020.

Abstract

Introduction: 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Brain / metabolism*
  • Brain / pathology*
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology*
  • CD4-CD8 Ratio
  • Disease Progression
  • Endothelium / metabolism
  • Endothelium / pathology
  • Fas Ligand Protein
  • Humans
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Membrane Glycoproteins / metabolism*
  • T-Lymphocyte Subsets / pathology*

Substances

  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins