Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroblastoma cell lines can have very low MHC Ag expression. The cell lines are insensitive to allo-killing by primed CTL, but are sensitive to non-MHC-restricted cytotoxicity. IFN-gamma increased class I expression, but the cells remained insensitive to CTL. Susceptibility to nonrestricted effectors was preserved. Class I+ glioma cell lines behaved similarly. The CTL resistance was localized to the recognition phase. Neuroblastoma lines did not form conjugates with primed T cells, but were lysed if they were coupled to the effectors via lectins. The levels of class I expression, and resistance to CTL, were constant over a range of IFN doses. HLA-A,B,C structure and distribution were studied more intensively on one cell line, CHP-100. HLA-A2 and -A3 were present on greater than or equal to 99% of the cells, in a unimodal distribution. After IFN treatment, the levels were similar to B cell controls. In two-dimensional gel electrophoresis, the molecules co-migrated with those of B cell controls. The defect may thus be in accessory proteins that are necessary for T cell recognition or binding, rather than in the structure or distribution of the HLA-A,B,C proteins.
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PMID:IFN-treated neuroblastoma cell lines remain resistant to T cell-mediated allo-killing, and susceptible to non-MHC-restricted cytotoxicity. 245 35

An extensive panel of monoclonal antibodies (MAb) and monospecific antisera reactive against neuroectodermal-, neuronal-, glial-, and lymphoid-associated antigens, extracellular matrix, HLA, and cell-surface receptors was used to characterize the phenotype of four continuous, karyotypically distinct medulloblastoma cell lines and transplantable xenografts. All four cell lines demonstrated significant reactivity with anti-neuroectodermal-associated MAb. No apparent pattern of reactivity with anti-lymphoid MAb was seen; notably, there was a uniform absence of detectable Thy-1. Review of the complete antibody reactivity profile revealed a dichotomy between lines TE-671 and Daoy and lines D283 Med and D341 Med, which have been previously shown to express neurofilament protein in culture and xenografts, and to exhibit neuroblastic morphological features in biopsy and xenograft tissue sections. TE-671 and Daoy reacted with the MAb directed against tenascin, epidermal growth factor (EGF) receptor, HLA-A,B epitopes, beta 2-microglobulin and 5/8 of the glioma-associated antigens, but did not react with the anti-neurofilament protein (NFP) MAb. D283 Med and D341 Med expressed NFP but did not react with MAb against tenascin, EGF receptor, HLA-A,B epitopes, beta 2-microglobulin or 6/8 and 7/8 (respectively) of the glioma-associated antigens. The observed phenotypic differences provide a conceptual framework for investigating basic differences in the biological behavior of medulloblastoma. Moreover, the subdivisions can be evaluated for prospective value in tissue diagnosis, cerebrospinal fluid cytology and antibody-mediated imaging and therapy.
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PMID:Phenotypic analysis of four human medulloblastoma cell lines and transplantable xenografts. 253 15

The antigenic heterogeneity of human neuroectodermal tumors defined by both murine and human monoclonal antibodies (MAs) is reported; no patterns of reactivity defining degree of anaplasia, in vitro morphology, or immunogen used were apparent. We investigated the reactivity of 20 distinct murine MAs defining markers of glioma-associated or predominantly lymphoid distribution for 13 human glioma-derived (HGL) cell lines and frozen sections of 19 human glioblastoma multiforme (GBM) and six astrocytomas (AST). Methods included radioimmunoassay, immunofluorescence, immunohistochemistry, and absorption analysis. Two markers, HLA-A,B and human Thy-1, exhibited no deviation; all HGL cell lines tested bound high levels of specific MA. Individual HGL cell line reactivity with the MA panel ranged from 30 to 70%. HGL cell lines (7/13) which reacted with greater than or equal to 50% of the antiglioma MAs had the highest (30-70%) positive reactivity rates with the anti-lymphoid marker MA panel; complex antigenicity in one system correlated with multiple antigens in the other. Within the anti-lymphoid marker MA panel, subpopulations of 4/13 HGL cell lines were clearly positive for the HLA-DR (Ia) antigens; another 3/13 HGL cell lines were strongly positive for common acute lymphocytic leukemia antigen (CALLA). With the exception of Thymocyte 1 antigen (Thy-1), reactivity for early and mature T-cell markers was infrequent and sporadic. Lymphoid marker expression by HGL cell lines is highly heterogeneous, ranging from few (Thy-1 and HLA-A,B) to complex expression of Ia, T-cell, and lymphoid tumor markers. GBM and AST tissues were antigenically less complex; for each of 6/8 anti-glioma MA, 70-100% of GBM and 66-100% of AST were positive. Two MAs were highly reactive (7/10, 8/9) with GBM sections and minimally so (1/6) with AST. Antigenic expression in gliomas is complex and heterogeneous; however, clear differences in lymphoid marker expression, the identification of widely and rarely expressed glioma-associated antigens, and the potential of immunologic differentiation between GBM and AST by large panels of MAs will serve to reduce the complexity and may be of potential diagnostic or prognostic significance.
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PMID:Antigenic heterogeneity of human anaplastic gliomas and glioma-derived cell lines defined by monoclonal antibodies. 258 Sep 59

Twenty-eight human brain tumors (18 gliomas and 10 metastatic brain tumors) were examined immunohistochemically using anti-Leu 1, -Leu 2 a, -Leu 3a + 3b, -LeuM 5, -HLA-DR, IL-2 receptor, -HLA-ABC and Ki-67 monoclonal antibodies (MoAb). Also, in the specimens, in which Leu 1+ cells and Leu M5+ cells infiltrate, simultaneous detection of Leu 2a, Leu 3a + 3b, or Leu M5 and HLA-DR, was performed by double immunofluorescence staining to analyze the T cell activation and antigen-present macrophage (M phi). Most of low-grade gliomas with low percentage of Ki-67+ cells showed only little lymphocyte and M phi's infiltration. THEre was a tendency toward a marked degree of T cell and M phi infiltration in malignant glioma with higher percentage of Ki-67+ cells. However, in metastatic brain tumors, M phi did not tend to infiltrate. IL-2 receptor+ cells was absent in the majority of brain tumors. Tumor cells and vascular endothelial cells also expressed HLA-DR antigens. The majority of tumor cells expressed HLA-A, B, C antigens. There were no correlation among the degree of T cell and M phi infiltration, MHC antigen expression, and percentage of Ki-67+ cells. Double immunofluorescence staining demonstrated that 42.4% of Leu 2a+ cells, 34.7% of Leu3a+ + 3b+ cells and 32.7% of M5+ cells are HLA-DR positive in glioma, and that 50.2% of Leu2a+ cells, 59.4% of Leu3a + 3b+ cells and 67.3% of LeuM5+ cells are HLA-DR positive in metastatic brain tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Analysis of activated lymphocytes and antigen-present macrophage in human brain tumors using double immunofluorescence staining]. 269 76

The modulation of HLA-DR and HLA-A, -B, and -C by human recombinant immune interferon (IFN-gamma) was studied on 10 malignant glioma cell lines established in our laboratory, on 8 clones or subclones derived from these lines, and on a fetal astrocyte cell line. Comparative studies were performed with recombinant leukocyte interferon (IFN-alpha). The results not only confirmed the selective activity of IFN-gamma on the modulation of HLA-DR expression, as opposed to that of IFN-alpha, but also demonstrated a marked heterogeneity in the response of glioma cell lines and their clones to the two types of IFN tested. For example, all 3 clones of an inducible cell line could be modulated to express HLA-DR, whereas only 2 of 5 clones derived from a noninducible line were modulated. This heterogeneity did not seem to be due to the absence of the receptor for IFN-gamma on the surface of these cells, since almost all of the cell lines or clones tested (17 of 19) responded to IFN-gamma by the induction or enhancement of the expression for either HLA-DR or HLA-A, -B, and -C (or both). The heterogeneity of induction was also demonstrated between clones derived from a glioma line that did not express HLA-DR after IFN-gamma treatment. The production of HLA-DR by one of the clones was abundant enough to be confirmed by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis.
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PMID:Heterogeneity of the induction of HLA-DR expression by human immune interferon on glioma cell lines and their clones. 308 Jun 35

Many immune responses are controlled by genes of the major histocompatibility complex (MHC). In humans these include the loci encoding the HLA-A, -B, -C, -DR, -DQ, and -DP antigens, and many diseases have been linked with these. However, little information is available about any connection between malignant tumors and HLA. In this study the possible association of HLA-A, -B, -C and -DR specificities with susceptibilities to malignant glioma was investigated in 42 patients with malignant glioma and 42 controls with non-glial intracranial tumors using the Terasaki-NIH standard method. The data were also compared with those of the 11th International HLA Workshop. The result showed that a high frequency of HLA-24(9) was observed in patients with intracranial malignant gliomas, which was not common in other, non-glial patient groups. In animals the MHC acts in defense against virally induced tumors, but until now there has been no evidence that they do so in human gliomas. Our discovery of its association with an HLA antigen is important for understanding the immunogenetic basis of susceptibility to glioma.
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PMID:Association of malignant glioma with the human leukocyte antigen, HLA-A24(9). 783

By flow cytometry, a panel of 18 primary glioma cell explants exhibited high expression of class I HLA-A, B, C, but class II HLA-DR expression was absent. Freshly isolated normal brain cells displayed little or no HLA antigens. Alloreactive cytotoxic T lymphocytes (aCTL), sensitized to the HLA of the patient, were generated in a one-way mixed lymphocyte response (MLR). The specificity of aCTL was confirmed to be to target cells (patient glioma cells or lymphoblasts) expressing the relevant HLA antigens. However, nontumor patient-specific aCTL did not lyse normal brain cells. Titration of antibodies to HLA class I into cytotoxicity assays blocked lysis of gliomas by aCTL, confirming aCTL T cell receptor (TCR) interactions with the class I antigen on gliomas. Furthermore, aCTL interactions with glioma cells caused their apoptosis. Coincubations of aCTL with gliomas resulted in upregulated cytokine secretion. Importantly, dexamethasone, an immunosuppressive steroid used for brain edema, did not affect aCTL lytic function against tumor, indicating that steroid-dependent patients may benefit from the immunotherapy. We also explored the use of interferon-gamma (IFN-gamma) to increase aCTL tumor recognition. Coincubation of gliomas with exogenous IFN-gamma (500 U/ml, 48 h) caused a 3-fold upregulation of HLA class I and a slight induction of class II antigen expression. Gene-modified glioma cells producing IFN-gamma similarly displayed upregulated HLA expression. Glioma cells incubated with exogenous IFN-gamma or IFN-gamma-transduced glioma cells were more susceptible to lysis by aCTL than their parental counterparts, thus supporting the concept of combining IFN-gamma cytokine gene therapy with adoptive aCTL immunotherapy for brain tumor treatment.
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PMID:Human alloreactive CTL interactions with gliomas and with those having upregulated HLA expression from exogenous IFN-gamma or IFN-gamma gene modification. 1451 64

Human immunodeficiency virus 1 (HIV-1) downregulates cell surface expression of HLA-A and HLA-B but not HLA-C or HLA-E to ultimately escape immune defences. Here, it is shown that cell surface expression of the non-classical HLA-G1 is also downregulated by HIV-1, by using co-transfection experiments and infection with cell-free HIV-1 of HLA-G1-expressing U87 glioma cells or macrophages in primary culture. Moreover, co-transfection experiments using proviruses deleted in either nef or vpu or plasmids encoding HIV-1 Nef and Vpu mixed together with a HLA-G1-expressing construct demonstrated that HLA-G1 downregulation is Nef-independent and Vpu-dependent, contrasting with the Nef- and Vpu-dependent HLA-A2 downregulation. Together, these results show that the decrease of HLA-A2 and HLA-G1 caused by HIV-1 occurs through distinct mechanisms.
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PMID:Human immunodeficiency virus 1 downregulates cell surface expression of the non-classical major histocompatibility class I molecule HLA-G1. 1521 79

Currently, peptide-based cancer vaccines are developed in many different groups, however, no sufficient clinical outcomes have been obtained. We have developed personalized peptide vaccine for advanced cancer patients with different types of HLA-A locus. Personalization of the vaccination peptides from the candidate peptide pool was conducted by considering the HLA types of patient and pre-existing levels of IgG to the candidate peptides. The personalized peptide vaccine for patients with hormone-refractory prostate cancer has been approved as innovative therapy by the Ministry of Health, Labour and Welfare, Japan. Here, we describe the recent progress of the personalized peptide vaccine particularly for patients with prostate cancer, bladder cancer, and malignant glioma.
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PMID:[Peptide-based cancer vaccine therapy for prostate cancer, bladder cancer, and malignant glioma]. 2192 70

Glioblastoma multiforme is the most frequent and most malignant primary brain tumor with poor prognosis despite surgical removal and radio-chemotherapy. In this setting, immunotherapeutical strategies have great potential, but the reported repertoire of tumor associated antigens is only for HLA-A 02 positive tumors. We describe the first analysis of HLA-peptide presentation patterns in HLA-A 02 negative glioma tissue combined with gene expression profiling of the tumor samples by oligonucleotide microarrays. We identified numerous candidate peptides for immunotherapy. These are peptides derived from proteins with a well-described role in glioma tumor biology and suitable gene expression profiles such as PTPRZ1, EGFR, SEC61G and TNC. Information obtained from complementary analyses of HLA-A 02 negative tumors not only contributes to the discovery of novel shared glioma antigens, but most importantly provides the opportunity to tailor a patient-individual cocktail of tumor-associated peptides for a personalized, targeted immunotherapeutic approach in HLA-A 02 negative patients.
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PMID:Natural HLA class I ligands from glioblastoma: extending the options for immunotherapy. 2326 46


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