Immunobiology of primary intracranial tumors. VI. Suppressor cell function and lectin-binding lymphocyte subpopulations in patients with cerebral tumors

Roszman, Thomas L.; Brooks, William H.; Elliott, Lucinda H.

doi:10.1002/1097-0142(19821001)50:7<1273::aid-cncr2820500709>3.0.co;2-5

Cited by 73 publications

(50 citation statements)

References 23 publications

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“…Patients with gliomas are characterized by systemic immune dysfunction, as shown by impaired cell-mediated immunity, lymphopenia (2,3,6), and inability to mount delayed-type hypersensitivity reaction (3). The degree of immunosuppression observed in glioma patients may correlate with tumor size and grade (35,36).…”

Section: Discussionmentioning

confidence: 99%

“…The tumor microenvironment has a deleterious effect on tumorinfiltrating T cells, and there is evidence that the immunosuppressive effects extend into the periphery as well (1). Even glioblastoma multiforme (GBM) that develops and remains usually within the brain can induce local and systemic host immunosuppression (2,3). This impairment of the immune system, specifically when it affects T lymphocytes, can occur through mechanisms that increase the sensitivity of these cells to apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Chahlavi¹,

et al. 2005

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“…Patients with primary malignant intracranial neoplasms exhibit broad suppression of immunocompetency as manifest through a variety of in vivo and in vitro determinants (1)(2)(3)(4)(5)(6)(7)(8)(9). Most notably, the T cell hyporesponsiveness observed in these patients is a result of the failure of these cells to enter and complete the proliferative cycle when compared to comparably stimulated T cells obtained from normal individuals (10).…”

Section: Introductionmentioning

confidence: 99%

Inability of mitogen-activated lymphocytes obtained from patients with malignant primary intracranial tumors to express high affinity interleukin 2 receptors.

Elliott

Brooks²,

Roszman³

1990

J. Clin. Invest.

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Patients with primary malignant brain tumors manifest a variety of abnormalities in cell-mediated and humoral immunity. Diminished T cell reactivity has been shown in these patients to be linked to deficiencies in interleukin 2 (IL-2) production that cannot be overcome by exogenous IL-2. In this study, specific binding of radiolabeled IL-2 to PHA-stimulated lymphocytes from brain tumor patients demonstrates that the number of high affinity interleukin 2 receptors (IL-2R) is greatly reduced. FACS analysis indicates that the relative density of the p55 protein (Tac protein) is lower on the mitogen-activated lymphocytes obtained from patients than on comparably treated lymphocytes from normal individuals. These data indicate that mitogen-stimulated lymphocytes obtained from patients have fewer functional high affinity IL-2R principally because of the failure to express sufficient levels of the p55 protein for association with the p75 protein. Northern analysis of total RNA isolated from mitogen-stimulated T cells from patients demonstrates normal levels of steady state mRNA, which codes for the p55 protein. Moreover, there is no defect in the postranslational processing of the primary translation product of this mRNA suggesting that normal levels of the p55 protein are produced in activated T cells from patients. (J. Clin. Invest. 1990. 86:80-86.)

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“…Peripheral blood lymphocytes from glioma patients proliferate poorly in response to T cell mitogens, anti CD3, and T and B cell dependent mitogens [46][47][48]. The total T cell compartment has limited capabilities to respond to mitogen stimulation [46,47,49,50].…”

Section: Immunosuppression In Gbmmentioning

confidence: 99%

Cellular Immunotherapy for Malignant Brain Tumors

Flores¹,

Mitchell²

2011

Brain Tumors - Current and Emerging Therapeutic Strategies

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Immunobiology of primary intracranial tumors. VI. Suppressor cell function and lectin-binding lymphocyte subpopulations in patients with cerebral tumors

Cited by 73 publications

References 23 publications

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

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

Inability of mitogen-activated lymphocytes obtained from patients with malignant primary intracranial tumors to express high affinity interleukin 2 receptors.

Cellular Immunotherapy for Malignant Brain Tumors

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