Relationship of lymphocyte invasion and survival of brain tumor patients

Brooks, William H.; Markesbery, William R.; Gupta, Garima; Roszman, Thomas L.

doi:10.1002/ana.410040305

Cited by 202 publications

(83 citation statements)

References 11 publications

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“…Some authors also observed that patients with more prominent lymphocytic infiltrates had a better survival (Brooks et al, 1978 andPalma et al, 1978). Using cell separation and flow cytometry, we identified CD3 + T cells in all tumours examined, but by immunohistochemistry observed CD3 + cells in only 6 of 9 GBM, a figure in keeping with previous histological studies (Bertrand andMannen, 1960 andvon Hanwehr et al, 1984).…”

Section: Discussionmentioning

confidence: 97%

T-cell apoptosis in human glioblastoma multiforme: Implications for immunotherapy

Walker

Chuah

Rist

et al. 2006

Journal of Neuroimmunology

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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 Tcell 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.

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Section: Discussionmentioning

confidence: 97%

T-cell apoptosis in human glioblastoma multiforme: Implications for immunotherapy

Walker

Chuah

Rist

et al. 2006

Journal of Neuroimmunology

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“…One role of T cells is to recognize and respond to neoplastic cells anywhere in the body including the central nervous system (27)(28)(29). Immune effector cells do enter the brain in response to molecules expressed by the endothelial cells and astrocytomas (30).…”

Section: Discussionmentioning

confidence: 99%

Glioblastomas Induce T-Lymphocyte Death by Two Distinct Pathways Involving Gangliosides and CD70

Chahlavi¹,

et al. 2005

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Here we report that glioblastoma multiforme (GBM) mediates immunosuppression by promoting T-cell death via tumorassociated CD70 and gangliosides that act through receptordependent and receptor-independent pathways, respectively. GBM lines cocultured with T cells induced lymphocyte death. The GBM lines were characterized for their expression of CD70, Fas ligand (FasL), and tumor necrosis factor-A (TNF-A), and the possible participation of those molecules in T-cell killing was assessed by doing GBM/T cell cocultures in the presence of anti-CD70 antibodies, Fas fusion proteins, or anti-TNF-A antibodies. CD70 but not TNF-A or FasL is responsible for initiating T-cell death via the receptor-dependent pathway. Of the four GBM cell lines that induced T-cell death, three highly expressed CD70. Two nonapoptogenic GBM lines (CCF3 and U138), on the other hand, had only minimally detectable CD70 expression. Blocking experiments with the anti-CD70 antibody confirmed that elevated CD70 levels were involved in the apoptogenicity of the three GBM lines expressing that molecule. Gangliosides were found to participate in the induction of T-cell apoptosis, because the glucosylceramide synthase inhibitor (PPPP) significantly reduced the abilities of all four apoptogenic lines to kill the lymphocytes. Highperformance liquid chromatography (HPLC) and mass spectroscopy revealed that GM2, GM2-like gangliosides, and GD1a were synthesized in abundance by all four apoptogenic GBM lines but not by the two GBMs lacking activity. Furthermore, gangliosides isolated from GBM lines as well as HPLC fractions containing GM2 and GD1a were directly apoptogenic for T cells. Our results indicate that CD70 and gangliosides are both products synthesized by GBMs that may be key mediators of T-cell apoptosis and likely contribute to the T-cell dysfunction observed within the tumor microenvironment. (Cancer Res 2005; 65(12): 5428-38)

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“…Increased infiltration of lymphocytes into gliomas has been associated with an improved prognosis in a number of reports, 9,20,45 although other studies have failed to confirm this finding. 10 Some of this discrepancy likely relates to failure to adequately identify the varying subpopulations of lymphocytes present within such tumors.…”

Section: Discussionmentioning

confidence: 99%

“…8,51 The role of these infiltrating immune cells is not clear, and both anti-tumor and pro-tumor effects have been suggested. Several early studies documented a better prognosis in patients with glial cell tumors and larger lymphocytic infiltrates, 9,20,45 although other studies failed to show such a benefit. 10 The heterogeneous nature of the infiltrating lymphocyte population may, in part, account for this discrepancy but was not examined in these reports.…”

mentioning

confidence: 99%

Characterization of Immune Cell Infiltration Into Canine Intracranial Meningiomas

et al. 2011

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Meningiomas are the most common intracranial tumors in dogs. A variety of inflammatory cells have been shown to invade these tumors in people, but little is known about interactions between the immune system and naturally occurring brain tumors in dogs. The purpose of this study was to investigate the presence of a variety of immune cell subsets within canine intracranial meningiomas. Twenty-three formalin-fixed, paraffin-embedded tumor samples were evaluated using immunohistochemistry with antibodies specific for CD3, CD79a, CD18, CD11d (aD), CD45RA, forkhead box P3, and Toll-like receptors 4 and 9. Immune cell infiltration was evident in all samples, with a predominance of CD3 þ T cells. Large numbers of CD18 þ microglia and macrophages were noted surrounding and infiltrating the tumors, and a subset of these cells within the tumor appeared to be CD11d

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Relationship of lymphocyte invasion and survival of brain tumor patients

Cited by 202 publications

References 11 publications

T-cell apoptosis in human glioblastoma multiforme: Implications for immunotherapy

T-cell apoptosis in human glioblastoma multiforme: Implications for immunotherapy

Glioblastomas Induce T-Lymphocyte Death by Two Distinct Pathways Involving Gangliosides and CD70

Characterization of Immune Cell Infiltration Into Canine Intracranial Meningiomas

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