Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278883 (metastatic melanoma)
 6,224 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MHC antigen expression on 20 nevi, and 35 primary and 95 metastatic melanomas was studied by immunoperoxidase techniques using monoclonal antibodies to identify the antigens on frozen tissue sections. DR antigens were not detected on nevi but were detected on 71% of primary melanomas and 56% of metastases, suggesting that this antigen may be a useful marker of malignant transformation of nevi. Expression of class II antigen could not be related to other prognostic histological features of primary melanoma such as tumour thickness, but comparison of the common phenotypes of primary and metastatic melanoma suggested that expression of DR antigens alone in the absence of DP, DQ and ABC antigens may be an indicator of metastatic potential. Class I (HLA-A,B,C) antigens were also expressed infrequently on nevi but were detected on 43% of primary melanomas and 34% of metastases. HLA-A,B,C expression was inversely related to thickness of the primary melanoma. This as well as the lower expression of class I antigens on metastases, may indicate that growth and spread of melanoma may be inhibited by MHC (class I) dependent cytotoxic T cell responses. Expression of class I MHC antigens was unrelated to class II antigens. Expression of DR was more common than DP or DQ, but the latter with one exception, were not expressed in the absence of DR antigens. Significant differences were not found in MHC antigen expression on metastases in lymph nodes compared to those in subcutaneous sites, but further studies are needed to determine whether such differences may exist between metastases in other visceral sites.
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PMID:Immunohistological evaluation of MHC class I and II antigen expression on nevi and melanoma: relation to biology of melanoma. 332 39

The roles of ultraviolet-B (UV) radiation in the immunogenicity of human cancer cells have not been fully studied. We have investigated the effects of UV radiation on metastatic melanoma and renal cell carcinoma cells with regard to MHC antigen expression and the ability to induce cytotoxic T lymphocyte (CTL) activity in peripheral blood mononuclear cells (PBMC) or tumor-infiltrating lymphocytes (TIL) against untreated autologous tumor cells. UV radiation respectively decreased or increased MHC class I expression of freshly isolated tumor cells or cultured tumor cells, and also decreased MHC class I expression of starved cultured tumor cells. It increased the ability of both freshly isolated and cultured tumor cells to induce CTL activity from PBMC against untreated autologous tumor cells. UV-irradiated subclones that were more susceptible to CTL lysis were more potent for CTL induction from TIL than either an untreated parental clone or a UV-irradiated subclone that was resistant to CTL lysis. In summary, UV radiation increased the ability of tumor cells to induce CTL activity without a corresponding effect on MHC antigen expression.
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PMID:Increase in the ability of human cancer cells to induce cytotoxic T lymphocytes by ultraviolet irradiation. 824 64

Specific antitumor immune responses require expression of MHC class I or II molecules on tumor cells, and MHC antigen down-regulation is a presumed tumor growth promoting mechanism. Because IFN-gamma up-regulates tumor MHC antigen expression in vitro, in this Phase II trial of an immunologically active dose and schedule we evaluated whether this was the case in vivo. Twenty-three patients with metastatic melanoma were treated with IFN-gamma 100 microg/m(2) s.c. once weekly for a maximum of 6 months. There were three complete responses, now maintained for 53, 36, and 25 months. The remainder had progressive disease. The treatment was well tolerated, with no toxicity exceeding National Cancer Institute Common Toxicity Criteria grade II. Immunohistochemical analysis of tumor biopsies during treatment was performed using monoclonal antibodies to HLA class I (W/632) and class II (CR3/43) monomorphic determinants. HLA class I was down-regulated in 2 of 19 patients pretreatment and up-regulated by IFN-gamma in both. HLA class II was down-regulated pretreatment in 14 of 18 patients and up-regulated by IFN-gamma in 6 (43%). The HLA up-regulation persisted throughout the study. IFN-gamma induced significant but short-lived up-regulation of surrogate markers of monocyte activation (serum neopterin) and class I up-regulation (serum beta-2-microglobulin) in most patients. There was no consistent relationship between surrogate marker up-regulation, tumor antigen up-regulation, and responses. The study shows that the significant immune modulation induced by IFN-gamma does not correlate with tumor responses and that the serum surrogate marker changes do not reflect tumor events. The durable and long-lived responses, clear demonstration of tumor MHC up-regulation, and low toxicity suggest that weekly IFN-gamma 100 microg/m(2) would be a useful addition to chemoimmunotherapeutic regimens.
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PMID:Low-dose IFN-gamma induces tumor MHC expression in metastatic malignant melanoma. 1253 55