Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the non-major histocompatibility-restricted cytotoxic activity induced by interleukin 2 (IL-2) and interferon alpha (IFN-alpha) in mononuclear cells of peripheral blood (PBMNC) from glioblastoma patients. We observed a depressed cytotoxic activity against natural killer (NK)-sensitive target cells in PBMNC from all the patients studied. Culture of these PBMNC with IFN-alpha for 5 days augmented the cytotoxic activity against NK-sensitive target cells in a small group of patients. Incubation with IL-2 for 5 days normalizes the decreased cytotoxic activity against NK-sensitive target cells of PBMNC from all the glioblastoma patients studied. When PBMNC from these patients were incubated with IL-2 for 5 days and IFN-alpha was added to the culture medium in the last 2 h of culture, an enhancement of non-major histocompatibility-restricted cytotoxic activity was observed compared with that obtained with either IL-2 or IFN-alpha alone. This improvement of the cytotoxic activity was more relevant when it was tested against NK-resistant target cells. The potential utility of the sequential use of the two cytokines in generating non-major histocompatibility cytotoxic activity in glioblastoma patients is discussed.
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PMID:Interleukin 2 and interferon alpha modulation of the lymphocyte non-major histocompatibility-restricted lytic activity in glioblastoma patients. 146 64

Human glioblastoma cells secrete a peptide termed glioblastoma-derived T cell suppressor factor (G-TsF) which inhibits T cell activation. Recently, purification and cloning of G-TsF revealed that G-TsF is identical to transforming growth factor-beta 2. As shown here, G-TsF suppresses the growth of an ovalbumin-specific mouse T helper cell clone (OVA-7T) independently of the stimulus used being either (a) antigen in the presence of antigen-presenting cells, or (b) interleukin 2 (IL2) or (c) phorbol ester and calcium ionophore. Furthermore, in the presence of antibodies against IL2 receptors, G-TsF was able to suppress the residual proliferation still observed when OVA-7T were stimulated with phorbol ester/ionophore. G-TsF failed to inhibit the release of IL3 from OVA-7T activated with IL2. Taken together, the data provide evidence that G-TsF does not directly interfere with interactions of IL2 with its receptor but rather inhibits T cell activation by interfering with an as yet unidentified pathway used by both IL2 and phorbol ester/ionophore. When analyzing different monokines and lymphokines for its effect on G-TsF-induced suppression of T cell growth the only factor found to partially neutralize the effect of G-TsF was tumor necrosis factor-alpha.
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PMID:The glioblastoma-derived T cell suppressor factor/transforming growth factor-beta 2 inhibits T cell growth without affecting the interaction of interleukin 2 with its receptor. 245 45

Glioblastoma cells release factors (G-TsF) which inhibit T-cell proliferation. The G-TsF is a novel member of the transforming growth factor beta family and is identical to TGF beta 2. The effect of G-TsF and TGF beta 2 on the induction of LAK cell activity was investigated by culturing PBL obtained from normal blood donors and brain tumour patients in varying concentrations (50-500 U/ml) of interleukin 2 (IL2) alone or IL2 plus G-TsF/TGF beta 2 (1 ng/ml) for 4 days. Subsequent cytolytic activity was measured against autologous and allogeneic glioblastoma targets, fresh NK-resistant melanoma cells and K562 cells. G-TsF/TGF beta 2 purified from glioblastoma cell cultures and TGF beta 2 isolated from porcine platelets significantly suppressed the generation of LAK cell activity, and the inhibitory effect could be reduced by higher concentrations of IL2. The suppressive effect of TGF beta 2 was most significant during the early stages of LAK cell generation and no inhibitory effect was seen when TGF beta 2 was added directly to the cytotoxicity assay. These results suggest that human glioblastomas may exert an inhibitory influence on the generation of an immune response in vivo through the production of G-TsF/TGF beta 2, and that the inhibitory effect may be modified by IL2.
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PMID:The glioblastoma-derived T-cell suppressor factor/transforming growth factor beta 2 inhibits the generation of lymphokine-activated killer (LAK) cells. 326 91

The human glioblastoma cell line 308 constitutively secretes a soluble factor with biologic and biochemical characteristics of human monocyte-derived interleukin 1 (IL 1). The 308 cells also produce a 97,000 m.w. factor that inhibits the effects of IL 1 and interleukin 2 (IL 2) on T lymphocytes. By using sequential chromatography on Blue Affigel, hydroxyapatite, and Ultrogel AcA54, the inhibitory factor, termed glioblastoma-derived T cell suppressor factor (G-TsF), was separated from IL 1 and purified 2000-fold with respect to the protein present in the crude 308 cell supernatant. This G-TsF preparation was sensitive to tryptic proteolysis, showed a peak of pI 4.6 on isoelectric focusing, and when labeled with 125I, revealed six protein bands in the range of 30 to 100 kdaltons on SDS gel.
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PMID:Partial purification and biochemical characterization of a T cell suppressor factor produced by human glioblastoma cells. 387 Dec 5

Studies were designed to investigate whether the cellular immunodeficiency state observed in human glioblastoma patients could be due to inhibitory factors released by the tumor cells. Cultured human glioblastoma cells were found to secrete an interleukin 1-like factor (m.w. 22,000) and a factor (m.w. 97,000) that inhibits interleukin 2 (IL 2)-dependent T cell mechanisms. This is demonstrated by its inhibitory effect on the IL 2-induced proliferation of T cell clones and on the induction of alloreactive cytotoxic T cells in mixed lymphocyte cultures. Additionally the glioblastoma cell-derived 97,000-m.w. factor inhibited growth of neuroblasts but not of fibroblasts and thus shares the characteristics of the neuroblast growth inhibition factor (NGIF) previously detected in the supernatant of fetal rat glia cell cultures. If released by glioblastoma cells in vivo, the factor may contribute to impaired immunosurveillance and to the cellular immunodeficiency state detected in the patients.
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PMID:Glioblastoma cells release interleukin 1 and factors inhibiting interleukin 2-mediated effects. 660 49

This study investigates a new approach to adoptive therapy of glioblastoma using as antitumor effector a potent major histocompatibility complex nonrestricted killer clone (TALL-104) established from a patient with acute T-lymphoblastic leukemia. The human glioblastoma cell line U-87 MG could be successfully engrafted in mice with severe combined immunodeficiency using the i.p., intracerebral, and s.c. routes. The latter model was elected to evaluate therapy based on its high reproducibility. Tumor growth in mice engrafted s.c. was proportionally associated with splenomegaly and leukocytosis. Multiple transfers of lethally irradiated (non-proliferating) TALL-104 cells at the tumor site resulted in about 50-70% inhibition of tumor growth as compared to untreated mice, with concomitant reduction of splenomegaly and leukocytosis. The antitumor effects were inversely proportional to the size of the tumor at initiation of therapy, 90-100% inhibition occurring in severe combined immunodeficiency mice treated from the day of U-87 MG challenge. Neither splenomegaly nor leukocytosis developed in animals in which tumor growth was completely blocked. Stimulation of TALL-104 cells with either interleukin 2 or interleukin 12 prior to irradiation and adoptive transfer increased the antitumor efficacy of the killer cells to about the same extent. The potential usefulness of irradiated TALL-104 cells in adjuvant therapy against glioblastomas and other well-localized tumors is discussed.
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PMID:Treatment of experimental glioblastoma with a human major histocompatibility complex nonrestricted cytotoxic T cell line. 780 48

Programmed death 1 (PD-1, CD279) and programmed death ligand 1 (PD-L1, CD274) are involved in generating tumor-associated immunosuppression by suppression of T-cell proliferation and interleukin 2 (IL-2) production and immune checkpoint inhibitors targeting these molecules are showing compelling activity against a variety of human cancers. PD-L1 expression has shown a positive association with response to PD-1 inhibition in noncentral nervous system (CNS) tumors, e.g., melanoma or non-small cell lung cancer, and is discussed as a potential predictive biomarker for patient selection in these tumor types. This review summarizes current knowledge and potential clinical implications of PD-L1 expression in glioblastoma. At present, the following conclusions are drawn: (a) functional data support a role for PD-1/PD-L1 in tumor-associated immunosuppression in glioblastoma; (b) the incidence of PD-L1-expressing glioblastomas seems to be relatively high in comparison to other tumor types, however, the reported rates of glioblastomas with PD-L1 protein expression vary and range from 61 to 88%; (c) there is considerable variability in the methodology of PD-L1 assessment in glioblastoma across studies with heterogeneity in utilized antibodies, tissue sampling strategies, immunohistochemical staining protocols, cut-off definitions, and evaluated staining patterns; (d) there are conflicting data on the prognostic role and so far no data on the predictive role of PD-L1 gene and protein expression in glioblastoma. In summary, the ongoing clinical studies evaluating the activity of PD-1/PD-L1 inhibitors in glioblastoma need to be complemented with well designed and stringently executed studies to understand the influence of PD-1/PD-L1 expression on therapy response or failure and to develop robust means of PD-L1 assessment for meaningful biomarker development.
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PMID:Clinical Neuropathology mini-review 6-2015: PD-L1: emerging biomarker in glioblastoma? 2650 38