title: T-cell apoptosis in human glioblastoma multiforme: implications for immunotherapy.
abstract: We used immunohistochemistry and flow cytometry to assess apoptosis in human glioblastoma multiforme (GBM). Our immunohistochemical study revealed apoptosis of glioma cells expressing glial fibrillary acidic protein and of CD3(+) T cells infiltrating GBM. To quantify and phenotype the apoptotic T cells, we performed flow cytometry on lymphocytes separated from GBM. The cells were stained with annexin-V-FLUOS/propidium iodide to identify apoptosis. We found that high proportions of both the CD4(+) and CD8(+) T cells were apoptotic. In particular, we found that T cells expressing Fas ligand (Fas-L, CD95L) were eight times more vulnerable to apoptosis than those not expressing Fas-L, which suggests that the T-cell apoptosis is induced by overactivation of the T-cell receptor, possibly in the absence of appropriate costimulation. Our results have implications for the design of immunotherapies for GBM.
authors.affiliation: Department of Neurosurgery, Royal Brisbane and Women's Hospital, c/- Post Office RBH, Herston, Q4029 Australia. David_Walker@health.qld.gov.au
authors.forename: David G
authors.initials: DG
authors.lastname: Walker
authors.forename: Teong
authors.initials: T
authors.lastname: Chuah
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rist
authors.forename: Michael P
authors.initials: MP
authors.lastname: Pender
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D005434:Flow Cytometry; D005909:Glioblastoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D020287:In Situ Nick-End Labeling; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology