Imbalances in T cell subpopulations in human gliomas

Bhondeley, M K; Mehra, Reeti; Mehra, N. K.; Mohapatra, Ashok K.; Tandon, P. N.; Roy, S. C. Dutta; Bijlani, Veena

doi:10.3171/jns.1988.68.4.0589

Cited by 40 publications

(20 citation statements)

References 17 publications

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“…Gliomas seem to lack expression of TNF-a and, in fact, elaborate soluble TNF receptors which down-regulate infiltration of immune-competent cells (38). In addition, several studies have suggested that glioblastoma multiforme patients have T-cell dysfunction (39,40). However, this is not supported by the current study because glioblastoma multiforme patients were found to exhibit memory adenovirus-specific T-cell responses, functional dendritic cells, and tumor-specific T-cell responses.…”

Section: Discussioncontrasting

confidence: 79%

Glioblastoma Patients Exhibit Circulating Tumor-Specific CD8+ T Cells

Tang¹,

Flomenberg

Harshyne³

et al. 2005

Clinical Cancer Research

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Purpose: There is growing interest in developing cellular immune therapies for glioblastoma multiforme, but little is known about tumor-specific T-cell responses. A glioblastoma multiformeŝ pecific T-cell assay was developed using monocyte-derived dendritic cells to present tumor antigens from the established glioblastoma multiforme cell line U118. Experimental Design: Peripheral blood mononuclear cells (PBMC) and tumor cells were obtained from nine patients with newly diagnosed brain tumors: five glioblastoma multiforme, two oligodendroglioma, one ependymoma, and one astrocytoma. PBMCs were incubated overnight with autologous tumor cells or autologous dendritic cells loaded with a U118 cell lysate, and responses were detected by IFN-g ELISPOTand cytokine flow cytometry assays.Results: PBMCs from all glioblastoma multiforme patients exhibited IFN-g responses to autologous tumor but not to HLA-mismatched U118 cells. Glioblastoma multiforme^specific IFN-g responses were primarily mediated by CD8+ Tcells and represented f2% of total CD8+ Tcells. Additionally, all glioblastoma multiforme patients responded to autologous dendritic cells loaded with U118 lysate but not with low-grade astrocytoma cell lysates. PBMCs from four patients with other brain tumor types and one normal donor failed to respond to U118 lysate^loaded autologous dendritic cells. These data indicate that the IFN-g responses to U118 lysate^loaded autologous dendritic cells are glioblastoma multiforme specific. Moreover, PBMCs stimulated 1 to 2 weeks with U118 lysate^loaded dendritic cells exhibited MHC class I^restricted cytotoxicity against autologous tumor cells. Conclusions: Glioblastoma multiforme patients exhibit circulating tumor-specific CD8+ T cells that recognize shared tumor antigens from the glioblastoma multiforme cell line U118. These data show that glioblastoma multiformes are immunogenic and support the development of immunotherapy trials.

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Section: Discussioncontrasting

confidence: 79%

Glioblastoma Patients Exhibit Circulating Tumor-Specific CD8+ T Cells

Tang¹,

Flomenberg

Harshyne³

et al. 2005

Clinical Cancer Research

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“…We found that GBM patients had lower levels of CD3 C T cells than controls, as in other reports, 34 and lower levels of CD4 C CD25 C T cells, but a trend toward higher numbers of Foxp3-positive T cells. GBM patients also had increased levels of CD4 C T cells that expressed CD57 but had lost CD28 expression, which may indicate increased proliferative instability and senescence.…”

Section: Discussionsupporting

confidence: 90%

Poor survival in glioblastoma patients is associated with early signs of immunosenescence in the CD4 T-cell compartment after surgery

et al. 2015

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$These authors share senior authorship.Keywords: cytomegalovirus, glioblastoma, immunosenescence, survival, T cells Abbreviations: GBM, glioblastoma multiforme; HCMV, human cytomegalovirus; PBMC, peripheral blood mononuclear cell; Valcyte, valganciclovir; WBC, white blood cell countPatients with glioblastoma multiforme (GBM) are immunosuppressed and have a broad range of immunological defects in both innate and adaptive immune responses. GBMs are frequently infected with human cytomegalovirus (HCMV), a virus capable of causing immunosuppression. In 42 HCMV-positive GBM patients in a clinical trial (VIGAS), we investigated T-cell phenotypes in the blood and assessed their relation to survival. Blood was collected before and 3, 12, and 24 weeks after surgery, and the frequency of T-cell subsets was compared with that in 26 age-matched healthy controls. GBM patients had lower levels of CD3 cells than the controls, but had significantly higher levels of CD4 C CD28 ¡ T cells before and 3 and 12 weeks after surgery and increased levels of CD4 C CD57 C and CD4 C CD57 C CD28 C T cells at all-time points. These T-cell subsets were associated with both immunosenescence and HCMV infection. GBM patients also had higher levels of gd T cells at all-times after surgery and lower levels of CD4 C CD25 C cells before and 3 weeks after surgery than healthy controls. Overall survival was significantly shorter in patients with higher levels of CD4 C CD28 ¡ T cells (p D 0.025), CD4 C CD57 C T (p D 0.025) cells, and CD4 C CD28 ¡ CD57 C CD28 ¡ T cells (p < 0.0004) at 3 weeks after surgery. Our findings indicate that signs of immunosenescence in the CD4 C compartment are associated with poor prognosis in patients with HCMV-positive GBMs and may reflect the HCMV activity in their tumors.

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“…Do these factors influence systemic immunocompetence? In glioma patients, peripheral lymphocyte counts (specifically CD3 + and CD4 + cells) were reduced in relation to healthy individuals as was pointed out by Bhondeley et al 1 recently. In our glioma patients, this finding holds true, even when it was not healthy volunteers but patients with benign extracerebral tumours who served as controls.…”

Section: Pathophysiologymentioning

confidence: 54%

Peri-operative changes of cellular and humoral components of immunity with brain tumour surgery

et al. 1994

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Nosocomial infections, which are not uncommon in neurosurgical intensive care medicine, may possibly be favoured by an impairment of immunological competence of the patient. In a prospective observational trial, we investigated several parameters of cellular and humoral immunity in 32 patients before and after resection of an intracranial tumour. We quantified the effects of operative procedure, dexamethasone pretreatment, and tumour type. Dexamethasone alone causes an increase of neutrophilic granulocyte count and monocytes, whereas IgG and eosinophilic granulocytes decrease as well as lymphocytes. CD4+ T lymphocytes (T helper cells) and CD8+ T lymphocytes (T cytotoxic/suppressor cells) were more severely affected than B lymphocytes. Dexamethasone and operation in combination act synergistically on T lymphocytes and IgG, while no synergism is obvious in other clinical test parameters. The skin sensitivity reaction was depressed accordingly. With intracerebral tumours (gliomas WHO grades II to IV), levels of T helper cells and eosinophilic granulocytes were lower, and levels of IgM and neutrophilic granulocytes were higher than with benign extracerebral neoplasms. Postoperative nosocomial infections of the lower respiratory tract occurred almost exclusively in patients subject to severe depression of T helper cells.

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Imbalances in T cell subpopulations in human gliomas

Cited by 40 publications

References 17 publications

Glioblastoma Patients Exhibit Circulating Tumor-Specific CD8+ T Cells

Glioblastoma Patients Exhibit Circulating Tumor-Specific CD8+ T Cells

Poor survival in glioblastoma patients is associated with early signs of immunosenescence in the CD4 T-cell compartment after surgery

Peri-operative changes of cellular and humoral components of immunity with brain tumour surgery

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