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)

Decreased expression of MHC class I molecules in tumor cells has been reported to be associated with enhanced malignancy both in human and murine tumors. This paper studies HLA-ABC and HLA-DR expression in 56 basal cell carcinomas. Our results show that these tumors have a heterogeneous expression of MHC class I molecules: 11% exhibit uniform staining of most tumor cells; 25% are only partially positive, and the remaining 64% are MHC class I negative. A positive correlation between the level of HLA-ABC molecule expression and the degree of histological differentiation has been found. The expression pattern of tumor cells with anti-class II monoclonal antibodies shows weak homogeneous staining in 5%, staining in only a few areas of the tumor in 32%, whereas 63% has no significant staining for MHC class II antigens. Most mononuclear cells infiltrating the tumor were T lymphocytes (CD-3 positive). Results also show that 68% of the tumors express class II molecules homogeneously in the infiltrate. The expression of class II antigens in infiltrating lymphocytes correlated with the level of class II expression in the tumor cells probably as a consequence of lymphokine production by activated T cells.
Invasion Metastasis 1991
PMID:HLA expression in basal cell carcinomas. 183 4

Previous studies have suggested that class II major histocompatibility (MHC) antigen expression on melanoma cells may influence immune responses against melanoma and the nature of lymphocytic infiltrates against the tumor. This question was examined further by immunoperoxidase studies on sections from 29 primary and 30 metastatic melanoma with monoclonal antibodies (MAbs) against different lymphocyte subsets. The results indicated that expression of MHC class II DR* antigens on melanoma cells was associated with increased overall lymphocytic infiltration and that this applied particularly to the CD8+ subset of T cells. The CR3 receptor (CD 11b) was expressed predominantly on T cells and not macrophages but infiltration by CD11b+ cells did not correlate strongly with DR expression on melanoma cells. Dual staining with MAbs to CD8 and CD11b revealed that, whereas most of the CD8+ cells in DR- primary melanoma and DR+ metastatic melanoma were CD11b+, only approximately 50% of the CD8+ cells in DR+ primary melanoma were also CD11b+. Expression of CD11b on T cells was reported to define a suppressor subset of T cells. If the latter is correct the present results suggest that DR expression on primary melanoma is associated with infiltration by the cytotoxic T cell subset, whereas in the absence of DR antigens and in metastases this subset is absent and the predominant subset appears to be CD8+ CD11b+ T cells with suppressor activity. The biologic and prognostic significance of these findings remains to be determined.
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PMID:Immunohistological relation between DR antigen expression on melanoma cells and infiltration by CD8+ T cells. 214 56

Polyclonal goat anti-idiotypic Abs directed against anti-human gastrointestinal carcinoma mAb GA733 were administered to 13 colon cancer patients who had their primary tumor and lymph node metastases removed before immunotherapy. Patients received four s.c. doses (0.5 to 8 mg each) of alum-precipitated anti-idiotypic Ab. Seven of the 13 patients produced anti-anti-Ids that bound specifically to the GA733 epitope on tumor cells and shared idiotopes with mAb GA733. In four of the seven responding patients, anti-Id therapy specifically modulated T cell responses. In two patients who did not demonstrate GA733 Ag/anti-Id-reactive T cells before therapy, anti-Id administration induced CD4+, MHC class II-dependent T cells that specifically proliferated in culture in response to stimulation with either anti-Id or GA733 Ag. In two other patients who did demonstrate Ag/anti-Id-reactive T cells before therapy, anti-Id administration transiently induced lymphocytes that suppressed the proliferative responses of cultured pretherapy lymphocytes to stimulation with anti-Id or GA733 Ag. Nine of the 13 treated patients showed no evidence of disease after 39 to 86 mo of observation. Five of these patients developed Ag-specific Ab3 and one had, in addition, a T cell response.
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PMID:Induction of antigen-specific T and B cell immunity in colon carcinoma patients by anti-idiotypic antibody. 767 38

Inadequate co-stimulation of tumor reactive T cells may contribute to the fact that antigenic tumors are not normally rejected by the immune system. We recently reported that the induction of profound unresponsiveness in a T cell clone by melanoma cells expressing MHC class II antigens may provide a mechanism for these tumor cells to escape immunosurveillance. Here we demonstrate that two T cell clones (sTC3 and sTS5) produced high amounts of IL-10 after being rendered anergic by autologous melanoma cells. Co-culture of these T cell clones with melanoma cell transfectants expressing B7, which failed to induce anergy, resulted in a significantly lower production of IL-10. IL-10 production by the anergic T cell clones correlated with an impaired ability to produce IL-2 in response to TCR mediated activation. Neutralization of IL-10 reduced the duration of T cell unresponsiveness from 14 to only 4 days, but inhibition of IL-10 production during initiation of anergy showed no effect on it. Induction of the unresponsive state, as well as the subsequent IL-10 production in sTC3 cells, could be prevented by the addition of cyclosporin A to the primary co-culture of sTC3 and the autologous melanoma. Taken together, these results indicate that IL-10 is important for maintenance of T cell anergy induced by contact with nonprofessional antigen presenting cells such as MHC class II+ melanoma cells. Furthermore, we were able to detect IL-10 in serum from melanoma patients and IL-10 mRNA in tumor infiltrating lymphocytes isolated from melanoma metastases, suggesting an in vivo relevance of our in vitro findings.
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PMID:Maintenance of clonal anergy by endogenously produced IL-10. 782 50

Early microdissemination of tumour cells determines the prognosis of patients with apparently localised non-small cell lung cancer (NSCLC). Monoclonal antibodies to epithelial antigens can now be used to detect single carcinoma cells present in mesenchymal secondary organs such as bone marrow or lymph nodes. The present study was designed to obtain insights into the potential role of the immune system in lymphatic and haematogenous microdissemination of NSCLC cells. Using immunohistochemical staining of primary NSCLC, we assessed the expression pattern of molecules mediating an efficient cellular immune response, that is, MHC class I and class II antigens and the intercellular adhesion molecule-1 (ICAM-1). All 58 patients evaluated were staged as free of overt metastases by conventional clinico-pathological screening. Isolated tumour cells in bone marrow or lymph nodes were identified with mAb CK2 to cytokeratin component No. 18 and mAb BerEp-4 to glycoproteins of 34 and 39 kd present on epithelial cells, respectively. MHC class I expression on primary tumours was reduced or absent in 6/10 (60.0%) patients with isolated cancer cells in lymph nodes as compared to 6/33 tumours (18.1%) without such tumour cell dissemination (P = 0.01). MHC class II molecules on primary tumours were detected in 1/10 (10.0%) patients with micrometastases to regional lymph nodes and in 10/33 (30.3%) patients without such a tumour cell spread. None of the 10 patients with nodal microdissemination expressed ICAM-1 on their primary NSCLC, while such expression was detectable in 12/33 (36.4%) patients without this dissemination (P = 0.01). In contrast, the detection of tumour cells in bone marrow was not correlated to the expression of any of these immunoregulatory molecules. Our data suggest that escape caused by deficient expression of MHC class I antigens and ICAM-1 on tumour cells may support homing or survival of disseminated tumour cells in lymphoid tissue.
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PMID:Expression of MHC molecules and ICAM-1 on non-small cell lung carcinomas: association with early lymphatic spread of tumour cells. 869 22

Mouse tumor cells transfected with syngeneic MHC class II genes are highly immunogenic in the autologous host, and induce a potent tumor-specific immunity against wild type tumor. Previous studies with sarcoma tumor cells expressing transfected class II gene products with truncated cytoplasmic domains suggested that during the process of tumor rejection costimulatory molecules are induced on the tumor cells, contributing to the cells' ability to stimulate immunity. In the present study we directly demonstrate that tumor cells containing full-length class II heterodimers are induced to express B7-1 and B7-2 costimulatory molecules during the rejection process. In contrast, tumor cells expressing class II heterodimers truncated for their cytoplasmic tails are not induced to express B7-1 and/or B7-2. Blocking the interaction of the induced costimulatory molecules with their corresponding receptors on T cells prevents tumor rejection. These results support the hypothesis that the cytoplasmic domain of the MHC class II molecule is involved in induction of costimulatory molecule expression, perhaps via intracellular signalling pathways. Because class II, B7 transfected tumor cells are such effective immunogens against ascites and solid tumors, they have also been tested in metastatic disease. K1735 and B16BL6 mouse melanomas, when transfected with syngeneic MHC class II and B7-1 genes, are significantly less metastatic than parental cells, and immunization with the transfectants protects against subsequent challenge with wild type tumor.
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PMID:Expression of MHC Class II and B7-1 and B7-2 costimulatory molecules accompanies tumor rejection and reduces the metastatic potential of tumor cells. 879 42

The metastatic process is characterized by a complex series of sequential steps involving constant interactions (mutual "cross-talks") of metastasized tumor cells with their microenvironment (lymphocyte, macrophages, endothelial cells, etc.) in target organs. These interactions determine the outcome of metastasis (either the eradication of metastatic cells or their increased proliferation and invasion). Recently developed methods of tumor and host cell analysis at the molecular level allow better elucidation of molecular mechanisms of metastasis and of immune mechanisms involved in antitumor responses. Direct modulation of these processes will probably increase the success of clinical cancer treatment. Here we review data (a) on the expression of some costimulatory (MHC class II, CD80, sialoadhesin) and adhesion (LFA-1, ICAM-1, VLA-4) molecules on both metastasized tumor cells and host cells and (b) on the production of a cytotoxic molecule, nitric oxide, by in situ activated Kupffer and endothelial cells in the process of liver metastasis. This study was performed with well-characterized murine ESbL T lymphoma cells transduced with the bacterial lacZ gene, which allows detection and quantification of metastases at the single cell level throughout lymphoma growth and metastasis. Experimental results are discussed in the context of recent literature.
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PMID:New insights into tumor-host interactions in lymphoma metastasis. 884 48

The present study was performed to investigate processes involved in circumvention of the immune system by advanced stages of tumor growth in the liver. The efficacy of Kupffer cells and pit cells against cancer cells was tested in vivo in an experimental model of colon carcinoma metastasis in rat liver. Liver tumors were induced by administration of CC531 colon cancer cells into the vena portae. After 3 weeks, livers were obtained and partly fixed for electron microscopic procedures or frozen in liquid nitrogen for enzyme and immunohistochemistry at the light microscope level. The activation status of Kupffer cells was studied by expression of Ia-antigen (MHC class II) and by measurement of glucose-6-phosphate dehydrogenase (G6PDH) activity in the cells in situ as a measure of production of reactive oxygen species. Large numbers of Kupffer cells were found in liver parenchyma surrounding colon carcinomas when compared with levels in control livers, but these cells were not activated. Large numbers of activated monocytes and macrophages, cytotoxic T cells but only a few pit cells were found to be recruited to the boundary between liver parenchyma and tumors or their stroma. In those areas where cancer cells invaded liver parenchyma, only newly recruited macrophages and some Kupffer cells were present but few cytotoxic T cells or pit cells were found. The low activation status of Kupffer cells both in terms of production of reactive oxygen species and Ia-antigen expression and the absence of significant numbers of pit cells at tumor sites suggest that Kupffer cells and pit cells do not play a significant role in advanced stages of tumor growth. High levels of prostaglandin E2 were detected in the parenchyma of livers containing tumors and transforming growth factor beta was detected in the stroma of the tumors, therefore suggest that cytotoxicity of newly recruited monocytes, macrophages and cytotoxic T cells may be limited in these stages because of local production of these immunosuppressive factors.
Clin Exp Metastasis 1996 Sep
PMID:Kupffer cells and pit cells are not effective in the defense against experimentally induced colon carcinoma metastasis in rat liver. 887 11

One in seventy randomly selected individuals is supposed to host an adrenal mass. The increasing number of incidentally detected adrenocortical adenomas requires the effective and reliable evaluation of dignity. So far this has been determined through a difficult multi-parametric analysis. Since MHC class II antigens are expressed in the normal adrenal cortex with a restriction to the zona reticularis, we examined 28 adrenocortical incidentalomas, 10 adenomas, 13 cortical carcinomas, 2 metastases, 10 controls as well as the adrenocortical carcinoma cell line NCI-H295 immunohistochemically for the expression of HLA class II antigens. We showed, that the majority of the adenomas still express class II antigens, whereas the expression is abrogated in all carcinomas examined. Our results indicate, that the detection of HLA class II positive tumour cells excludes malignancy. Therefore, MHC class II antigens may serve as a novel tumour marker in the evaluation of dignity in adrenocortical tumours. These findings could change the strategy for the assessment of adrenal masses.
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PMID:MHC class II expression--a new tool to assess dignity in adrenocortical tumours. 895 65

Constitutive expression of major histocompatibility complex (MHC) class II molecules is normally restricted to professional antigen-presenting cells (APCs) of the immune system, although it also occurs frequently in melanoma. Clinical evidence suggesting that MHC class II expression by melanoma is associated with tumor progression led us to postulate a role for MHC class II-mediated antigen presentation in this disease. First, we investigated whether melanoma cells derived from metastases can process antigen and/or present peptide vi MHC class II molecules to a peptide-specific CD4+ T-cell clone. In all cell lines tested, melanoma cells were able to process antigen and present peptide efficiently to CD4+ T cells, resulting in T-cell proliferation increased 5-26-fold over controls. Next, we found that CD28-mediated costimulation was not required, because blocking with CTLA-4Ig had no effect on the T-cell response to either melanoma or B cells as APCs. In contrast, blocking CD54 (ICAM-1) resulted in a decrease in proliferation in response to peptide presentation by melanoma but not B cells. These data demonstrate that MHC class II molecules on melanoma cells are functional and that antigen-processing pathways are intact. In addition, CD54 seems to play a significant role in peptide presentation by melanoma.
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PMID:MHC class II-mediated antigen presentation by melanoma cells. 904 57


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