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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autologous tumor-specific cytotoxic T-lymphocytes (CTLs), generated by repeated stimulation with autologous melanoma and expanded in interleukin 2, are major histocompatibility complex restricted. These CTLs recognize a common tumor-associated antigen in the presence of HLA class I determinants, suggesting that allogeneic melanomas which express the restricting HLA-A region antigen could substitute for the autologous tumor in the generation of CTLs. This was investigated in the HLA-A2 system. Four T-cell lines were established by stimulation of lymphocytes with either autologous tumor or an HLA-A2-matched allogeneic melanoma. Allogeneic stimulated CTLs specifically lysed the autologous tumor and demonstrated an identical pattern of HLA-A2 restriction, when compared to the autologous stimulated CTLs. Lysis by the allogeneic stimulated CTLs was blocked by a monoclonal antibody to HLA class I antigens; lysis was also inhibited by both autologous tumor or HLA-A2 allogeneic melanomas when evaluated in cold target competition studies. The allogeneic stimulated CTLs proliferated in response to both autologous tumor and HLA-A2 melanomas, but not in response to HLA-A2 nonmelanomas. By phenotypic analysis these CTLs were CD3+ and predominantly CD8+ cells. We conclude that autologous tumor-specific CTLs can be generated using HLA-A region-matched allogeneic melanomas for stimulation. Since established, HLA-typed melanoma tumor lines can be used in the absence of autologous tumor; this procedure can be applied clinically to a broad patient population and may prove useful in the adoptive immunotherapy of melanoma.
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PMID:Generation of human autologous melanoma-specific cytotoxic T-cells using HLA-A2-matched allogeneic melanomas. 240 72

This study investigates the nature and specificity of cytotoxic T lymphocytes (CTL) in patients with melanoma which are able to kill autologous melanoma cells. Interleukin 2 (IL2)-dependent T cell clones from two melanoma patients and a normal subject were generated in mixed lymphocyte cultures (MLC) or mixed lymphocyte tumor cell cultures (MLTC) and propagated for prolonged periods in tissue culture. Analysis of their phenotype by a wide range of monoclonal antibodies (M.Abs) revealed two main phenotypes which depended on whether they expressed Fc receptors detected by Leu 11 M.Abs or not. Leu 11- T cells (referred to as Type 1) were inhibited by M.Abs to T3, T8, and a common HLA, ABC antigen. Conversely Leu 11+ T cells (referred to as Type 2) were inhibited by M.Ab to Leu 11 but not by M.Ab to T3, T8 and the HLA, ABC antigen. Subtypes among Type 1 cells were recognized which depended on their specificity. The most restricted were CTL [Type 1(a)] clones generated only in MLTC which recognized the autologous melanoma cell plus 1 of 11 other melanoma target cells. Type 1(b) CTL clones recognized a larger proportion (approximately 50%) of the melanoma cells. A third category [Type 1(c)] recognized antigens on melanoma cells shared with that on the EBV-transformed B cells used as stimulators in the MLC. Type 2 CTL clones had broad specificity to melanoma and nonmelanoma cells, characteristic of that described for lymphokine activated killer (LAK) cells. The latter were MHC unrestricted but further studies are required to clarify whether the Type 1 CTL clones are MHC restricted or not. The CTL activity of all clones was inhibited by M.Ab to the sheep red blood cell receptor and to the T10 antigens. It is suggested that recognition of these different types of CTL clones may assist future studies on the immune response against melanoma and the nature of antigens recognized by CTL.
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PMID:Clonal analysis of cytotoxic T lymphocytes (CTL) against autologous melanoma. Classification based on phenotype, specificity and inhibition by monoclonal antibodies to T cell structures. 242 40

We studied the mechanisms of resistance to interferon (IFN) in two human melanoma cell lines, SK-MEL-28/beta cells resistant to human recombinant beta-interferon (ReIFN-beta) and SK-MEL-28/gamma cells resistant to human recombinant gamma-interferon (ReIFN-gamma). SK-MEL-28/beta cells were resistant to both ReIFN-beta and IFN-alpha, but not ReIFN-gamma or natural gamma-interferon (IFN-gamma), and SK-MEL-28/gamma cells were resistant to both ReIFN-gamma and IFN-gamma, but not ReIFN-beta or IFN-alpha. SK-MEL-28/s cells, sensitive to both ReIFN-beta and ReIFN-gamma, had receptors for ReIFN-beta and ReIFN-gamma. Furthermore ReIFN-beta and IFN-alpha shared the common receptors as judged by competition assays, while the receptors for ReIFN-gamma were independent in SK-MEL-28/s cells. The Kd values of binding of both IFNs to SK-MEL-28/beta or SK-MEL-28/gamma cells were essentially equivalent to those to SK-MEL-28/s cells. Both labeled IFNs were internalized rapidly into all cell lines at 37 degrees C. No significant difference in internalization was found between IFN-sensitive and -resistant cells. Each cell line expressed HLA-AB and Mr 97,000 protein antigens, the expressions of which were enhanced by ReIFN-beta and ReIFN-gamma. Partial resistance to the enhancement of both antigens by both IFNs was seen in the resistant cells. Finally ReIFN-gamma, but not ReIFN-beta, induced a Mr 56,000 protein in SK-MEL-28/s cells. This effect of ReIFN-gamma was also detected in SK-MEL-28/beta cells, but not SK-MEL-28/gamma cells. These results provide some information concerning the nature of IFN-resistant cells. The receptors had no significant correlation with the resistance, while the expression of HLA-AB or Mr 97,000 protein antigens or the induction of proteins had some correlation with the resistance.
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PMID:Analysis of receptors, cell surface antigens, and proteins in human melanoma cell lines resistant to human recombinant beta- or gamma-interferon. 243 Jun 91

Immunohistochemical analysis for non-polymorphic determinants of HLA class I or class II antigens has been greatly facilitated by the use of monoclonal antibodies. Studies on the distribution of these antigens in tumour lesions emphasize their role in the tumour-host interaction and in tumour histopathology, especially as additional markers in the assessment of prognosis of melanoma patients. Changes in the expression of HLA antigens on tumour cells in vitro as induced by gamma-interferon may also occur in vivo as a result of local production by the T lymphocytic infiltrate in tumours.
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PMID:Expression and susceptibility to modulation by interferons of HLA class I and II antigens on melanoma cells. Immunohistochemical analysis and clinical relevance. 243 74

CTL clones isolated from PBL or from tumor-infiltrating lymphocytes (TIL) of a melanoma patient (pt665) were screened for specificity on a panel including autologous tumor cells from two distinct metastases (Me665/1, Me665/2), autologous EBV-transformed B cells and 15 allogeneic cell lines of different histology. Each clone displayed a peculiar cytolytic activity ranging from lysis of most targets (PBL clone 4C4) to preferential reactivity on the two autologous metastases (TIL clone 8B3). Blocking and modulation experiments, revealed that the lysis of autologous-Tu cells by TIL clone 8B3, but not by PBL clone 4C4, could be inhibited by mAb to HLA-class I and to CD3 Ag or by CD3 complex modulation. Clone 8B3 was tested also on a panel of 25 tumor clones from Me665/2, revealing that only 4 neoplastic clones were lysed (2/4, 2/14, 2/17, and 2/51). Cold target competition experiments indicated that the uncloned autologous melanomas and one tumor clone (2/17), but no two other tumor clones (2/10, 2/15), could compete with one another for lysis by 8B3. Determination of melanin content of tumor clones from Me665/2 revealed that the four neoplastic clones recognized by 8B3 possessed much lower melanin levels than all the other 20 clones not lysed by this effector.
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PMID:Cytotoxic T lymphocyte clones from peripheral blood and from tumor site detect intratumor heterogeneity of melanoma cells. Analysis of specificity and mechanisms of interaction. 246 23

The present studies were undertaken to characterize Ag presentation by cultured human melanoma cell lines. Cell lines established from "biologically early" lesions of malignant melanoma were able to present the soluble Ag tetanus toxoid (TT) to autologous and HLA-DR-matched allogeneic, TT-immune T cell clones. Proliferation of T cell clones in response to Ag presented by primary melanoma peaked on day 2 of culture with Ag. Ag presentation was blocked by pretreatment of TT-pulsed and fixed melanoma cells with mAb against HLA-DR, but not HLA-DQ, HLA-DP, or HLA-ABC. Ag processing and presentation were inhibited by treating the melanoma cells with ammonium chloride. In parallel with previous findings from this laboratory demonstrating the inability of cell lines cultured from "advanced" primary or metastatic melanoma to induce autologous T cell proliferation, such cell lines also failed to present this exogenous Ag despite the presence of cell-surface HLA-class II molecules. Thus, in contrast to the finding in biologically early melanoma, none of the multiple TT-immune, T cell clones from autologous patients or HLA-DR matched donors was able to respond to TT presented by melanoma cells cultured from advanced disease. Co-incubation studies revealed that metastatic melanoma cells did not secrete inhibitory substances during the APC assay, however, they were able to process TT, rendering it "immunogenic" in the presence of fixed, autologous non-T cells. When fixed, autologous melanoma cells were assayed for their ability to present processed Ag; fixed cells of early but not advanced disease were able to present Ag in this setting, indicating that the presenting limb becomes flawed in the evolution of the metastatic phenotype. Finally, studies of chloroquine inhibition of the capacity of melanoma cells derived from early primary disease to stimulate autologous peripheral blood T cells suggest that such cells process and present tumor-associated Ag in the same fashion as the "model" Ag TT.
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PMID:Defective antigen presentation by human melanoma cell lines cultured from advanced, but not biologically early, disease. 246 32

This study analyzed 1) the relationship between the molecules recognized by anti-intercellular adhesion molecule-1 (ICAM-1) mAb RR 1/1 and by anti-96K melanoma-associated Ag mAb CL203.4 in lymphoid cells, 2) the induction of ICAM-1 on activated PBMC, and 3) the functional activity of distinct and spatially distant determinants recognized by mAb CL203.4 and RR1/1. Sequential immunoprecipitation experiments showed that the determinant recognized by mAb CL203.4 is expressed on a slightly broader population of ICAM-1 molecules than that defined by mAb RR1/1. Serologic and immunochemical assays have shown that ICAM-1 is induced on lymphocytes activated with Con A, PHA-M, IL-2, allogeneic HLA mismatched lymphocytes and autologous PHA-M-activated T cells. However, ICAM-1 was not detected on lymphocytes incubated with IFN-gamma. Incubation of monocytes with LPS induced ICAM-1 in the subpopulation which lacks it and increased its density on the cells which express it. Induction of ICAM-1 is an early event in the activation process and precedes the appearance of IL-2 and transferrin receptors. Comparison of the functional activity of the anti-ICAM-1 mAb CL203.4 and RR1/1 showed that both of them inhibit to a similar extent proliferation of lymphocytes stimulated with PHA-M and with allogeneic lymphocytes, but that only mAb RR1/1 inhibits PMA-induced aggregation of cultured B lymphoid cells JY, of promonocytic cells U-937 and of PHA-blasts as well as LAK cell-mediated cytotoxicity of target cells. mAb CL203.4 represents the first example of anti-ICAM-1 mAb without inhibitory effect on the aggregation of lymphoid cells. The differential functional activity of mAb CL203.4 and RR1/1 does not reflect differences in their affinity, because they display a similar affinity constant to lymphoid cells. These results suggest that distinct determinants of ICAM-1 play a different role in immunologic phenomena.
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PMID:Differential role of distinct determinants of intercellular adhesion molecule-1 in immunologic phenomena. 247 35

The authors studied the expression of CD1 and HLA-Dr antigen in benign and malignant melanic tumors to known if were the melanoma's cells or Langerhans cells, presents on the tumor, which exhibited the HLA-Dr antigens, and if the HLA-Dr expression was related to volume, depth and metastatic characteristics. These antigens were studied with the monoclonal antibodies labelled to avidin-biotin-peroxidase system. The results shows than the proportion between the number of Langerhans cells and HLA-Dr positive cells is inverse. No differences were found between the expression of the HLA-Dr antigens and number of Langerhans cells and volume, depth or metastatic characteristics.
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PMID:[Expression of HLA-Dr and CD1+ cells in malignant and benign pigmentary tumors]. 247 14

HLA class I and II expression was studied on 244 (177 primary and 67 metastatic) solid human tumours of different origin. Alkaline immunophosphatase (APAAP) and immunoperoxidase were used on cryostatic sections to stain MHC antigens. Monomorphic MoAbs were used against class I heavy chain, beta 2-microglobulin, DR, DQ and DP molecules. Class I expression was homogeneous on colon, melanoma and epidermoidal primitive tumours. Loss of HLA class I antigens was more frequent on basal cell carcinomas and sarcomas and was related to tumour differentiation on larynx carcinoma. Class I expression was heterogeneous on breast, larynx and stomach primitive neoplasias. Class I negative tumours were more frequent on metastatic than on primitive melanomas. Divergence of class I between primary tumours and autologous metastases was observed on melanomas, larynx and colorectal carcinomas. Class II expression was heterogeneous on all tumours and in a large number of cases was associated with high intensity of leukocytic infiltrate. HLA-DR expression was higher than HLA-DP and HLA-DQ (DR greater than DP greater than DQ) and was related to tumour progression. Four human tumour cell lines were modulated with recombinant interferon-gamma for HLA class I and II antigens. Different HLA profiles were obtained: increased class I and II expression, increased class II or a low response. Finally, class I genes from 22 tumours were compared with autologous normal cells by Southern blot analysis: 12 tumours were class I positive and 10 negative. No clear differences in RFLP were observed that could be associated with class I rearrangement. The results are discussed in relation to the role that histocompatibility antigens may play in tumour progression and invasiveness.
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PMID:Phenotypic expression of histocompatibility antigens in human primary tumours and metastases. 249 52

The effect of leukocyte (IFN-alpha), fibroblast (IFN-beta), and immune (IFN-gamma) interferon and/or mezerein on the expression of HLA antigens and melanoma-associated antigens by the melanoma cell line MeWo and its metastatic variant MeM 50-10 was investigated, since this information may contribute to our understanding of the molecular mechanism(s) underlying the metastatic process and of the role of cell differentiation and growth suppression in the antigenic changes induced by interferon (IFN). The three types of IFN had no effect on the expression of high-molecular-weight melanoma-associated antigen, but enhanced that of HLA Class 1 antigens and of intercellular adhesion molecule 1 on MeWo and MeM 50-10 cells. The enhancing effect of IFN-gamma was more marked than that of IFN-alpha and IFN-beta. Furthermore IFN-gamma enhanced the expression of intercellular adhesion molecule 1 by MeM 50-10 cells more than by MeWo cells. IFN-beta was shown for the first time to induce HLA Class II antigens; the effect of IFN-beta, like that of IFN-gamma, is differential on the two cell lines and on the gene products of the HLA-D region. Like IFN-gamma, IFN-beta induced only HLA-DR antigens on MeM 50-10 cells. The results of Northern blot analysis with HLA-DR beta, -DQ beta, and -DP beta probes suggest that the differential modulation of the gene products of the HLA-D region by IFN-beta and IFN-gamma reflects transcriptional and posttranscriptional events. The differential susceptibility to modulation by IFN-beta and IFN-gamma of HLA Class II antigens on MeWo and MeM 50-10 cells is an intrinsic property of each cell line, since only small differences were detected in the number and/or affinity of receptors on the two cell lines. Furthermore, the lack of marked effects of mezerein on the antigen-modulating activity of the three types of IFN, in spite of an enhancement of their differentiating activity, suggests that the changes in the antigenic profile induced by IFN do not represent a differentiation-related phenomenon.
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PMID:Modulation by interferons of HLA antigen, high-molecular-weight melanoma associated antigen, and intercellular adhesion molecule 1 expression by cultured melanoma cells with different metastatic potential. 249 70


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