Intratumoral T cell subset ratios and Fas ligand expression on brain tumor endothelium.
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.
Yu
John S
JS
The Marine Dunitz Neurosurgical Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA.
Lee
Paul K
PK
Ehtesham
Moneeb
M
Samoto
Ken
K
Black
Keith L
KL
Wheeler
Christopher J
CJ
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*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins