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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A decreased expression of major histocompatibility complex (MHC) class I antigens is a common feature of many experimental and human tumors and can often be correlated with malignancy grade. In fact, reduction of class I antigens is associated in most tumors with an enhanced ability to elude immune surveillance. Loss of HLA-A,B,C antigens ranges from a decrease in the percentage of A,B,C-positive cells to selective loss of particular antigens and total loss of class I molecule expression. In man, this has been documented in melanomas, carcinomas, lymphomas, neuroblastoma and acute leukemias. The reduction in membrane antigens is generally associated with a parallel fall in immunoprecipitable intracellular proteins and the corresponding mRNAs in the absence of structural changes in the coding genes. The literature concerning the above mentioned topics is reviewed and discussed.
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PMID:Expression of HLA class I antigens in human tumors and their involvement in tumor growth. 219 65

Genomic amplification of the oncogene N-myc is associated with rapid tumor progression and poor prognosis in patients with neuroblastoma (NB). However, 40% of NBs which lack N-myc amplification are also clinically aggressive. Factors other than N-myc copy number must therefore play a role in determining tumor progression in these NBs. We have established an unusual human NB cell line (NBL-S) from the primary tumor of a patient with rapidly progressive disease which lacks N-myc amplification. The doubling time in vitro (48 h) and the time from injection of 2 x 10(7) cells to detectable tumors in nude mice (46 days) in similar to NB cell lines with amplified N-myc. However, karyotype analysis reveals no evidence of double minutes (DMs), homogeneously staining regions (HSRs), or chromosome 1p deletions, features commonly seen in NB cell lines. The cells have the cell surface phenotype typical of N-myc amplified NB (HLA-A,B,C negative and HSAN 1.2 positive), and similar to other NB cell lines, N-myc RNA and protein are expressed. Interestingly, the half-life of the N-myc protein in NBL-S is prolonged (approximately 100 min) compared to the short N-myc protein half-life previously described in N-myc amplified NB cell lines (approximately 30 min). Because N-myc protein is thought to have a regulatory role, prolongation of the half-life of this protein may be an important factor in the regulation of growth in NBs which lack N-myc amplification and rapidly progress.
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PMID:Prolonged N-myc protein half-life in a neuroblastoma cell line lacking N-myc amplification. 228 1

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

Human neuroblastoma cells lack HLA-A,-B,-C molecules which can be induced in vitro by gamma interferon (gamma IFN). To test the hypothesis that the same induction would occur in vivo leading to tumor regression, a Phase I study was initiated. Seven patients with neuroblastoma were entered on a Phase I study of recombinant gamma IFN in children. Three received 0.05 mg/m2 intravenously (IV) three times a week, three received 0.1 mg/m2 for 4 weeks, and one patient withdrew from study before receiving adequate treatment for evaluation. No significant clinical response was seen. The side effects were fever and chills, and no serious toxicity occurred. Natural killer (NK) and lymphocyte activated killer (LAK) precursor activity of peripheral blood mononuclear cells was determined before and during treatment, and expression of HLA-A,B,C molecules was looked for on the tumor cells in the bone marrow of five patients. The NK activity initially low, reached control levels in six patients, but the increase was transient. The LAK precursor activity remained normal. Expression of HLA-A,B,C, initially absent, was induced on the neuroblastoma cells in four of six patients.
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PMID:The effects of gamma interferon on the natural killer and tumor cells of children with neuroblastoma. A preliminary report. 250 18

Gamma-interferon (IFN-gamma) increases class I major histocompatibility complex (MHC) expression in human neuroblastoma cell lines. These cells are of interest because of the initial paucity of MHC expression, a paucity that is also seen in neural tumors and normal brain. The aim of this study was to define further the class I molecules, and to begin to analyze the genetic basis of the regulation. Northern blot analysis with cDNA probes for HLA and beta 2-microglobulin (beta 2-m) RNAs shows that both are present in reduced quantities (relative to a B-cell control) in control neuroblastoma cells. The levels of both RNAs are increased following IFN-gamma. This behavior parallels that of the corresponding polypeptides. Further monoclonal antibody analysis of the class I proteins from IFN-treated cells shows that both HLA-A and HLA-B are present. For two cell lines, expression of appropriate polymorphic specificities is also shown to be increased. We conclude that IFN-gamma can cause increased expression of appropriate HLA-A,B,C specificities on cells of neuronal origin. This raises the question of whether these molecules can serve predicted immunological functions.
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PMID:Interferon-mediated induction of class I MHC products in human neuronal cell lines: analysis of HLA and beta 2-m RNA, and HLA-A and HLA-B proteins and polymorphic specificities. 309 12

The susceptibility of human neuroblastoma cells to direct cellular cytotoxicity has not been previously established. This is of particular interest because of their aggressive growth and low HLA expression. Neuroblastoma lines CHP 100 and CHP 126 were found to be excellent targets in 4-hr CML assays. Natural killer (NK) cells from fresh PBL and from an NK clone, 3.3, have high lytic activity against both cell lines. We also studied mixed lymphocyte culture-generated cytotoxic lines containing allo-specific cytotoxic T lymphocytes (CTL) directed against HLA antigens present on the neuroblastoma target cell lines. These lines did show excellent lytic activity, but cold target competition studies indicated that all of the lysis resulted from NK activity. This was verified by using inhibition studies with the use of monoclonal antibodies. OKT 3 and anti-HLA antibodies that block CTL function caused no reduction in kill. In contrast, anti-lymphocyte function antigen-1 (anti-LFA-1), which blocks both NK and CTL function, significantly inhibited lysis. These results serve as a functional confirmation of earlier findings of a very weak expression of HLA-A,B,C and beta 2-microglobulin on neuroblastoma cells.
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PMID:Human neuroblastoma cell lines are susceptible to lysis by natural killer cells but not by cytotoxic T lymphocytes. 315 2

In these studies, strong HLA-A,B,C or b2-m expression was not detected in any stage of development of normal neurons. These included regenerating cells of the olfactory epithelium, developing neural tissue in the mouse embryo, and normal adult brain. Nor was an obligatory role for HLA-A,B,C or b2-m revealed by in vitro analysis of a growing neuroblastoma cell line.
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PMID:Biological significance of HLA-A,B,C expression in neuroblastoma and related cell lines. 340 9

Monoclonal antibodies to beta 2-microglobulin (beta 2m), and to the native two-chain molecule, were used to assess the expression of the HLA-A, B, C molecules on human neuroblastoma-derived cell lines. In radioimmuno-, cytotoxic, and microscopic assays, employing fresh and fixed cells, neuroblastoma cells show at best weak activity as compared to glial or lymphoid cells. In binding inhibition assays, neuroblastoma extracts were 200- to 1800-fold less efficient in inhibiting the antibodies than were glial or lymphoid extracts. Immunoprecipitation and SDS-PAGE analysis confirmed that a beta m-like chain is synthesized by the neuroblastoma cells, but the HLA chain could not be visualized by this technique. HLA-A, B, C and beta 2m levels are known to vary among tissues and cell lines. Yet the magnitude of the differences between the neuroblastoma and lymphoid lines is much greater than the reported differences in expression between some of these same lymphoid lines and many other nonlymphoid malignant or nonmalignant cell types. Metastatic neuroblastoma tumor in bone marrow also showed weak HLA-A, B, C activity, with the cells appearing negative in microscopic assays. Possible clinical implications are discussed.
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PMID:Striking paucity of HLA-A, B, C and beta 2-microglobulin on human neuroblastoma cell lines. 618 60

IFN-gamma is known to induce expression of Ia antigens on a variety of cell types. In the present study, this activity of IFN-gamma has been analyzed with a panel of 36 melanoma cell lines, normal melanocytes, and 97 cell lines representing a range of other differentiation lineages. 55% of the melanoma cell lines express Ia antigens in a constitutive manner without IFN-gamma induction. Of the 16 Ia-melanoma lines, 13 could be induced to express Ia antigens by IFN-gamma, whereas three were noninducible. Melanocytes, which do not normally express Ia antigens, are converted to Ia expression by IFN-gamma. Ia antigens expressed constitutively or after IFN-gamma induction were identified with antibodies detecting monomorphic and allomorphic products of DR and DC loci. IFN-gamma appeared to be unique in its ability to induce Ia expression on melanoma and melanocytes; 14 other agents (including IFN-alpha and IFN-beta) known to influence growth or differentiation did not have Ia-inducing activity. Equally striking is the restriction of antigenic changes following IFN-gamma induction to HLA-associated products; of the 38 systems of cell surface antigens examined, only HLA-A,B,C, beta 2m, and Ia antigens were affected. A variety of other Ia- cell types were shown to be Ia-inducible by IFN-gamma; these included established lines of breast, colon, pancreas, bladder, kidney, ovary, and brain cancers, and cultures of normal fibroblasts, kidney epithelia, and epidermal keratinocytes. In contrast, three tumor types, teratocarcinoma, choriocarcinoma, and neuroblastoma, were not inducible for Ia expression, even though IFN-gamma could induce expression of HLA-A,B,C products. The broad representation of Ia antigens on most somatic cell types expressed either constitutively or after IFN-gamma can be viewed in an immunological context (antigen presentation/immune regulatory signals) or could indicate that Ia products have functions other than those related to immune reactions.
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PMID:Surface antigens of melanoma and melanocytes. Specificity of induction of Ia antigens by human gamma-interferon. 620 1

Previous work showed that each of four human neuronal cell lines expresses less than or equal to 0.5% of the HLA-A,B,C and beta 2-microglobulin seen in glial, lymphoid, and other cell types, and there is a corresponding weak expression in neuroblastoma tumor and adult brain. Here, we probe the genetic basis of this weak expression. For each of three neuroblastoma cell lines, we show that HLA-A,B,C and beta 2-microglobulin can be induced by interferon and that the induction occurs within every cell of the population. Class II (Ia) molecules are not detected. Microscopic assay and radioimmunoassay of intact cells suggest that the induced antigen appears at the cell surface as well as within each cell. Immunoblot analysis confirms that the induced proteins have the structure of class I molecules. Thus, the normal weak HLA and beta 2-microglobulin expression of these cell lines appears to reflect a regulatory control rather than a primary genetic lesion. According to current theory, lack of HLA-A,B,C should protect transformed, infected, or damaged neurons--but also neurons in neural transplants--from T-cell-mediated immunosurveillance. The possibility that neuronal HLA-A,B,C expression may be under regulatory control is of importance in this context.
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PMID:Weak HLA and beta 2-microglobulin expression of neuronal cell lines can be modulated by interferon. 643 14


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