Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between major histocompatibility complex (MHC) antigens and metastasis was investigated on B16 melanoma variants. B16 cell lines express low amounts of murine MHC (H-2) antigens. A high expression can be induced in line B16-A by in vitro treatment with immune interferon (IFN-gamma) or by in vivo transplant in allogeneic mice. The increase of H-2 antigens correlated with an enhancement of lung colonization in young syngeneic mice. The higher metastatic capacity of B16-A cells with induced high levels of H-2 antigens was observed also in adult mice and in young mice pretreated with cyclophosphamide. These results were confirmed investigating the behaviour of a mutant B16 clone (B78H1) which was selectively resistant to the H-2-inducing action of IFN-gamma: lung colonization ability was not increased by IFN pretreatment. The study of variants derived from individual B16-A lung colonies revealed a wide range of H-2 levels. Variants with a low expression had a low colonization ability; one out of two variants with a high H-2 expression also was poorly colonizing. IFN-gamma-mediated H-2 expression appeared to act as an enhancer, rather than a determinant of B16 metastatic capacity.
Clin Exp Metastasis
PMID:Interferon-mediated enhancement of metastasis. Are MHC antigens involved? 311 68

The capacity of different cytokines to upregulate major histocompatibility complex (MHC) expression on murine tumor cells in vitro, and on s.c. tumors or pulmonary metastases in vivo has been examined. Interleukins-1, -2, and -4 (IL-1, -2, -4), tumor necrosis factor-alpha (TNF-alpha), alpha-interferon (IFN-alpha), and gamma-interferon (IFN-gamma), were incubated with tissue culture lines of murine tumor cells displaying low (MCA-101), intermediate (MCA-102, -106), or high (MCA-105) Class I expression. IFN-alpha and IFN-gamma significantly increased Class I but not Class II antigens on all lines. TNF-alpha, IL-1, -2, and -4 had no significant effect on Class I or II expression in vitro. Mice bearing pulmonary metastases or s.c. lesions generated by MCA-101 and -102 were treated with IFN-alpha or IFN-gamma i.p. or i.v., or with a single dose of TNF-alpha i.v. Immunoperoxidase staining of lung metastases or subcutaneous tumors showed an increase in Class I but not Class II expression on MCA-102 tumors treated with IFN-alpha or IFN-gamma. IL-1, -2, or TNF-alpha had no effect on MHC Class I or II expression in vivo. None of the cytokines tested could upregulate MHC Class I or II expression on MCA-101 tumors in vivo. Flow cytometry analysis demonstrated an increase in Class I but not Class II expression on MCA-102 and MCA-106 tumor cells from s.c. tumor treated with IFN-alpha or IFN-gamma. A kinetic analysis of the flow cytometry data revealed that augmented MCA-102 Class I levels persisted for several days after cessation of in vivo therapy with IFN-alpha. Our data suggest one possible mechanism for the synergistic antitumor effects of IL-2 and IFN-alpha.
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PMID:Modulation of murine tumor major histocompatibility antigens by cytokines in vivo and in vitro. 313 84

The melanoma-associated antigen P3.58 is rarely found on benign proliferating melanocytes but is consistently expressed on advanced malignant melanomas which have a high probability of metastasis. Previous studies have shown that its expression on normal tissues is limited to vascular endothelia and lymphoid follicle germinal centers and that it is also expressed by activated monocytes in vitro. In the studies reported here, anti-P3.58 monoclonal antibodies (mAb) were shown to partially inhibit antigen-specific and anti-CD3-induced T cell proliferation and to completely block a lymphocyte/monocyte clustering which occurs in the absence of added antigen. This inhibition is highly specific for P3.58 mAb and was not affected by mAb directed to major histocompatibility complex or T cell antigens. P3.58 therefore seems to be involved in an antigen-independent attraction or adhesion of lymphocytes. P3.58 is the second example (HLA-DR being the first) of an association between the expression of an immune function-associated molecule and the development of metastatic disease in melanoma.
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PMID:The tumor progression-associated human melanoma antigen P3.58 mediates monocyte-lymphocyte interactions in vitro. 322 Jan 5

A number of studies show that major histocompatibility complex (MHC) genes control host immune responses to viral-induced chicken tumors. The MHC gene-controlled responses to malignant neoplasms caused by Rous sarcoma virus, lymphoid leukosis virus and Marek's disease virus are reviewed. Genes that determine regression of Rous sarcomas and resistance to development of lethal Marek's disease lymphomas appear to map within the B-F region of the MHC. In some cases, genetic complementation of both MHC genes and non-MHC genes may be responsible for regression of tumors. Metastasis of Rous sarcoma cells is also influenced by the host's MHC genotype. Background genes can modify the specific MHC gene effect on resistance to progressive growth of Rous sarcomas and Marek's disease lymphomas. Studies showing that MHC-restricted immunity may be important in cytotoxic T cell reactions to virus-infected and/or transformed chicken cells are discussed. The MHC-restricted cytotoxicity, whereby the T cells and target cells must share one MHC haplotype for in vitro killing to occur, suggests that the T cells have receptors that recognize virus-altered self MHC antigens. This may be an important immune surveillance mechanism for limiting the proliferative growth of virus-induced tumors in chickens.
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PMID:Influence of the major histocompatibility complex on tumor regression and immunity in chickens. 330 46

Immunohistochemical analysis of subpopulations of inflammatory cells in 81 primary and secondary human brain tumors was done. Natural killer (NK) cells, representing non-major histocompatibility complex-restricted, spontaneous cytotoxicity and monocytic cells are virtually absent in infiltrates of gliomas and account only for a minor percentage of inflammatory cells in brain metastases of carcinoma and in craniopharyngeomas. Infiltrates in gliomas consist almost exclusively of T-cells of the suppressor/cytotoxic type whereas infiltrates in carcinoma metastases and craniopharyngeomas contain considerable numbers of T-helper/inducer cells and B-cells. From this the authors conclude (1) that NK cells do not play a major role in tumor rejection, and (2) that the kind of inflammatory reaction does not depend upon the tumor site but more likely on the tumor type. No correlation between tumor differentiation and infiltrate composition is evident.
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PMID:Inflammatory infiltrates and natural killer cell presence in human brain tumors. 333 36

The mechanism by which tumor allografts escape host immunologic attack was investigated. B16-BL6 cells (the bladder 6 subline of the B16 melanoma) (H-2b) were transfected with a gene (Dd) encoding an allogeneic class I major histocompatibility complex antigen. Clones that expressed Dd antigen were injected into the footpads of nonimmune syngeneic mice, syngeneic immune mice, and nude mice. Under conditions of immunologic selection a clone that contained multiple copies of the transfected gene formed variants that lacked the transfected gene. Primary tumors and pulmonary metastases of immunized mice and pulmonary metastases of nonimmunized mice had lost the Dd gene and, in most cases, all of the associated plasmid. In contrast, in immunodeficient nude mice, primary tumors and pulmonary metastases retained the Dd gene and the associated plasmid. Deletion of genes encoding cell surface antigens may be one of the mechanisms by which allogeneic tumors escape immunologic attack.
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PMID:In vivo immunologic selection of class I major histocompatibility complex gene deletion variants from the B16-BL6 melanoma. 347 58

Fifty-two patients with thyroid epithelial cell cancer were studied for evidence of association with human leukocyte antigens (HLA). Twenty-eight patients (53.8%) and 19.4% of 160 controls were HLA-DR1-positive, conferring a relative risk of 4.85 (chi 2 = 21.3, P less than 0.0001). HLA-DR1 was increased in all histologic types of thyroid cancer. Interestingly 10 of 12 patients with metastatic disease were DR1-positive compared to 18 of 41 patients without metastases (relative risk = 6.1, chi 2 = 4.7, P less than 0.05). This study suggests that major histocompatibility complex-linked gene(s) determine susceptibility to and the biologic behavior of thyroid cancer.
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PMID:The relation of susceptibility to and biologic behavior of thyroid epithelial cell cancer to HLA-DR1. 348 8

The adoptive transfer of lymphokine-activated killer (LAK) cells in conjunction with the systemic administration of recombinant interleukin 2 (RIL-2) results in the regression of established pulmonary and hepatic micrometastases from a variety of immunogenic and nonimmunogenic murine tumors in syngeneic C57BL/6 mice. Recent studies have shown that this therapeutic approach can mediate the regression of cancer in humans as well. Because of the practical difficulties in obtaining syngeneic or autologous LAK cells for the therapy of cancer in humans we have now evaluated the antitumor efficacy of allogeneic LAK cells generated from different strains of mice. The in vitro lysis of fresh tumor targets by LAK cells is not a major histocompatibility complex-restricted phenomenon since LAK cells of BALB/c-H-2d, DBA/2-H-2d, and C3H-H-2k origin all exhibited lytic activity when tested against allogeneic MCA-102-H-2b tumor cells in short term 51Cr release assays. In vivo, the i.v. transfer of allogeneic LAK cells combined with i.p. injections of RIL-2 reduced the number of established pulmonary metastases induced by either MCA-105 or MCA-101 tumors which are syngeneic to C57BL/6 hosts. The extent of reduction of these pulmonary metastases by the allogeneic LAK cells was directly dependent upon the dose of RIL-2 given; increasing doses of systemically administered RIL-2 resulted in increasingly greater reduction in the numbers of established 3-day pulmonary sarcoma metastases. In dose titration experiments, adoptive transfer of at least 2 doses of 10(8) allogeneic LAK cells was necessary to achieve significant antitumor effect in vivo. Allogeneic LAK cells were also successful in mediating significant regression of hepatic micrometastases. Again, the i.v. transfer of allogeneic LAK cells had a smaller therapeutic benefit compared to i.v. transfer of syngeneic LAK cells. When allogeneic LAK cells were injected intraportally, however, they were as effective as syngeneic LAK cells. Allogeneic LAK cells had little, if any, therapeutic effect on established pulmonary and hepatic metastases when administered to recipients previously immunized to the histocompatibility antigens on the donor cells. Taken together, our results indicate that allogeneic LAK cells from several strains of mice are effective in lysing fresh MCA-102 tumor in vitro and that when given i.v. in sufficient numbers, in conjunction with RIL-2, they can mediate significant reduction in the number of established pulmonary and hepatic micrometastases in nonalloimmunized C57BL/6 mice.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of immunotherapy with allogeneic lymphokine-activated killer cells and recombinant interleukin 2 on established pulmonary and hepatic metastases in mice. 348 26

Lyt-1+, L3T4a+ autoreactive cloned T cells, producing lymphotoxin (LT) and interferon-gamma (IFN-gamma) in response to self-class II major histocompatibility complex antigen in vitro were examined for their anti-tumor effect in vivo against B16 melanomas. Without the aid of exogenous interleukin 2, the autoreactive T cells, when injected immediately and at an equal cell number into the site of s.c. inoculated B16 melanoma cells inhibited tumor growth in sublethally irradiated and nonirradiated syngeneic mice. The autoreactive T cells also induced regression of tumors established 3 days earlier. Normal spleen cells or class II-restricted cloned T cells specific for chicken gamma-globulin (CGG) had no inhibitory effect on tumor growth. A single injection of autoreactive T cells delayed tumor growth and prolonged the survival of mice that had received a lethal dose of B16 melanoma cells. The autoreactive T cells caused extensive necrosis at the injection site. A treatment regime consisting of two successive injections of anti-I-Ab monoclonal antibody 3JP prevented the inhibition of tumor growth, supporting the hypothesis that the autoreactive T cells inhibited the growth of melanomas by releasing LT and IFN-gamma upon recognition of I-A antigen-bearing cells at the injection site. The CGG-specific control T cells did not cause necrosis and survived within the nests of uninhibited tumor cells. Autoreactive T cells administered i.v. immediately after i.v. injection of B16 melanoma cells markedly reduced pulmonary metastases, whereas CGG-specific T cells did not. These results indicate that autoreactive T cells can function in vivo as inhibitors of tumor growth.
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PMID:Anti-tumor activity of class II MHC antigen-restricted cloned autoreactive T cells. II. Novel immunotherapy of B16 melanomas by local and systemic adoptive transfer. 349 92

Clones of the T10 sarcoma, originated in a (H-2b X H-2k)F1 mouse, differ in their metastatic competence, correlated with differences in the expression of antigens of the two parental haplotypes. In fact, the metastatic phenotype is determined by the H-2Dk antigen. Whether the different major histocompatibility complex gene products control the metastatic phenotype via their different immunogenic properties was tested. The involvement of the immune system in controlling the development of metastases was inferred from experiments in which nonmetastatic T10 cloned cells were found to produce both experimental and spontaneous metastases in syngeneic immune-suppressed mice. After the testing of T-cell-mediated immune responses, metastatic T10 cloned cells, which expressed the H-2Db and H-2Dk antigens, were nonimmunogenic in their syngeneic hosts, whereas nonmetastatic T10 cloned cells, which expressed predominantly the H-2Db antigens, evoked a strong T-cell response. H-2Db and H-2Dk antigens expressed on T10 cells appeared to differ in their immunogenicity. This was further supported by the observation that whereas a good antibody response was elicited by H-2Db antigens expressed on T10 cells, only a low anti-H-2Dk antibody was produced. The different T10 cloned cells were not susceptible to natural killer (NK) activity in an in vitro assay, yet in vivo studies suggested the participation of NK activity in controlling T10 metastasis. In animals with depressed NK activity, metastases were generated even by nonmetastatic clones, whereas in animals in which NK activity was elevated, even metastatic clones failed to generate metastases. Both T-cell-mediated immune responses, probably restricted by the H-2D products and NK reactivity, appeared to participate in controlling the development of metastases by T10 cells.
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PMID:Metastatic capacity of cloned T10 sarcoma cells that differ in H-2 expression: inverse relationship to their immunogenic potency. 389 52


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