Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

LFA-3, ICAM-1, HLA.ABC and HLA.DR expression was analyzed on 66 neuroblastoma specimens. HLA.ABC was expressed on 26 specimens, HLA.DR on 2, LFA-3 on 20 and ICAM-1 on 10. HLA.ABC and LFA-3 were positive on ganglioneuroblastoma or ganglioneuroma, but they were negative on neuroblastoma, independently of the clinical staging; HLA.ABC and LFA-3 were induced in vivo by chemotherapy in parallel with tumoral cell differentiation, in both the primary and the metastases. The expression of ICAM-1 was restricted to 5 of the 10 low-grade stage-1 or stage-2 specimens, 1 stage-3 specimen, and the primary tumors of 2 patients with stage-4 disease, analyzed hence at diagnosis and after chemotherapy (4 specimens); metastatic cells obtained in 1 of these patients were negative. HLA.ABC and LFA-3 expressed on both mycN-negative and -positive specimens, whereas ICAM-1 was restricted to MYCN-negative specimens. LFA-3 diffusely stained partially differentiated neuroblasts, Schwann cells and ganglion cells. The expression of HLA.ABC on differentiated neuroblasts varied from one sample to another and within the same tumor; Schwann cells were strongly positive, but ganglion cells were negative. In positive samples, ICAM-1 was expressed on differentiated neuroblasts and Schwann cells, but negative on ganglion cells; however, most of the differentiated tumors were ICAM-1-negative, suggesting ICAM-1 induction by unknown local signal. The 4 markers were negative on undifferentiated neuroblasts. The distribution of these 4 markers on clinical specimens was in agreement with their reactivity on fetal tissues, as well as with results obtained on neuroblastoma cell lines before and after in vitro treatment with IFN-gamma.
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PMID:Expression of leucocyte adhesion molecules on 66 clinical neuroblastoma specimens. 171 Jun 8

Tumor-infiltrating lymphocytes (TiL) and autologous peripheral blood lymphocytes (PBL), mainly from breast and kidney tumor patients were cultivated with high- and low-dose rIL-2 under addition of autologous tumor cells or nonmalignant epithelial cells. Tumor cells added to TIL-cultures induced an additional proliferative response. Before cultivation, CD8+ and CD25+ lymphocytes were more frequent in TIL when compared to PBL, while CD16+, CD19+ and CD56+ cells were rare. After culture, lymphocytes of both origins showed an increase of CD2+, CD25+, CD56+ and HLA-DR+ cells and a relative decrease of CD3+ cells. The CD4+/CD8+ ratios and a number of CD56+ cells were rIL-2 dose dependent.
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PMID:Phenotyping of human tumor-infiltrating lymphocytes before and after exposure to different in vitro stimulation conditions. 171 82

Three autotumor-reactive T-cell clones have been established from tumor-infiltrating lymphocytes isolated from a metastatic lesion of human gastric carcinoma in the liver. The clones all were shown to be CD3+, CD8+, CD4-, CD16-, T-cell receptor alpha/beta +, and T-cell receptor gamma/delta-, and they have retained both their autotumor reactivity and the same phenotype for over a year in culture. Each clone had a different rearrangement of the T-cell receptor gamma chain genes as indicated by Southern blot analysis. Tested against a panel of 18 tumor cell targets, the clones preferentially lysed autologous tumor (AuTu) cells, but each clone also showed weak cytotoxicity against one allogeneic cholangiocarcinoma cell line. At the same time, each clone showed appreciable cytotoxicity against K562 targets. In blocking experiments, anti-CD3, anti-WT31, anti-CD8, or anti-HLA class I monoclonal antibodies blocked AuTu cytotoxicity but not cytotoxicity against K562. In contrast, allocytotoxicity against the cholangiocarcinoma was blocked only by anti-CD3 monoclonal antibody. All 10 subclones of one T-cell clone had high levels of AuTu cytotoxicity but variable levels of anti-K562 cytotoxic activity. Proliferation of the T-cell clones was significantly stimulated by the addition of irradiated autologous but not allogeneic tumor cells. Preincubation of cultured AuTu cells with tumor necrosis factor alpha or gamma-interferon (IFN-gamma), but not with IFN-alpha, increased their susceptibility to lysis by the T-cell clones; however, it increased resistance of AuTu to lysis by interleukin 2-activated natural killer cells. The expression of an adhesion molecule, intercellular adhesion molecule 1, on the surface of AuTu was also up-regulated by tumor necrosis factor alpha or IFN-gamma, but not by IFN-alpha. All three cytokines up-regulated HLA-class-I antigens on AuTu. Pretreatment of K562 targets or allogeneic cholangiocarcinoma cells with the same cytokines increased their resistance to lysis by the T-cell clones. Overall, the results indicate that these T-cell clones show specificity for AuTu but also independently recognize a limited number of allogeneic tumor targets and lyse K562 targets. The mechanisms involved in the recognition by the T-cell clones of autologous, allogeneic, and K562 tumor targets appeared to be distinct.
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PMID:Characterization of human autotumor-reactive T-cell clones obtained from tumor-infiltrating lymphocytes in liver metastasis of gastric carcinoma. 171 96

We analyzed the cytotoxicity and characterized the phenotype of oncolytic bone marrow (BM) lymphocyte subsets generated in vitro by interleukin-2 (IL-2) and stimulator cells (SC). Two irradiated B-lymphoblastoid cell lines (Daudi and EBV-transformed BSM) and fresh human acute myelogenous leukemia (AML) were used as SC. Stimulation with Daudi and IL-2 resulted in a substantial increase in cytotoxic activity (100- to 1000-fold) against a broad range of tumor targets, and total cellular expansion was higher compared to stimulation with IL-2 alone. The most prominent increase was observed in the CD16+ and CD56+/CD3- natural killer (NK) cell subset; however, a significant increase was also observed in CD56+/CD3+ T cells. Functional analysis of Daudi- and IL-2-generated subsets using fluorescence-activated cell sorting (FACS) revealed that most of the lytic activity was mediated by NK cells. Significant potentiation of oncolytic activity and cell growth was also seen in the cultures stimulated with BSM or fresh AML and IL-2. The highest oncolytic activity in the latter cultures was mediated primarily by CD8+, CD3+, and CD56- T cells, although NK cells also participated in cytotoxic activity. The T cell-mediated cytotoxicity was restricted by the major histocompatibility complex (MHC), since most cytotoxicity could be blocked by HLA I antibodies. Additionally, we observed that optimum stimulation of cytotoxicity required effector cell-stimulator cell contact. These data indicate that depending on the tumor used for stimulation, different lymphocyte subsets may be generated in IL-2 cultures. These different approaches may be useful in both specific and nonspecific immunotherapy.
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PMID:Generation of MHC-nonrestricted and restricted oncolytic subsets from human bone marrow. 172 69

Three predominantly CD8+ CTL lines, TIL 501, TIL 620, and TIL 660, were generated from three HLA-A2+ melanoma patients by culturing tumor-infiltrating lymphocytes in 1000 U/ml IL-2. These tumor-infiltrating lymphocytes lysed 12 of 18 HLA-A2+ autologous and allogeneic melanomas, but none of 20 HLA-A2-negative melanomas. They also did not lyse the MHC class I negative lymphoma-leukemia cell lines, Daudi, K562, or HLA-A2+ non-melanoma cell lines including PHA or Con A-induced lymphoblast, fibroblast, EBV-transformed B cell, Burkitt's B cell lymphoma, and colon cancer cell lines. Autologous and allogeneic melanoma lysis was inhibited by anti-CD3, by anti-MHC class I, and by anti-HLA-A2 mAb, indicating recognition of shared tumor Ag among melanoma cell lines in a TCR-dependent, HLA-A2-restricted manner. Six HLA-A2-negative melanoma cell lines obtained from five HLA-A2-negative patients were co-transfected with the HLA-A2.1 gene and pSV2neo. All 17 cloned transfectants expressing cell surface HLA-A2 molecules, but none of 12 transfectants lacking HLA-A2 expression, were lysed by these three HLA-A2-restricted, melanoma-specific CTL. Lysis of the HLA-A2+ transfectants was inhibited by anti-CD3, by anti-MHC class I, and by anti-HLA-A2 mAb, indicating recognition of shared tumor Ag on transfectants in a TCR-dependent, HLA-A2-restricted manner. These results identify the HLA-A2.1 molecule as an Ag-presenting molecule for melanoma Ag. They also suggest that common melanoma Ag are expressed among melanoma patients regardless of HLA type. These findings have implications for the development of melanoma vaccines that would induce antitumor T cell responses.
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PMID:Shared human melanoma antigens. Recognition by tumor-infiltrating lymphocytes in HLA-A2.1-transfected melanomas. 172 79

Human melanoma is an immunogenic neoplasm whereby enhancement of specific cell-mediated immunity can alter tumor progression. HLA-A2-restricted CTL have been demonstrated to kill allogeneic HLA-A2-matched melanoma. We investigated the ability of allogeneic melanoma cells sharing HLA-A antigens to sensitize melanoma patients' lymphocytes to induce HLA-A-restricted CTL to autologous melanoma. PBL from melanoma patients were cocultured with autologous melanoma cells in defined "cocktail medium" to generate melanoma-specific HLA-A-restricted CTL lines. CTL generated by sensitization with allogeneic melanoma bearing shared HLA-A2, A11, A24, or "cross-reactive" HLA-A antigens could kill almost as many autologous melanoma cells as CTL sensitized with autologous melanoma. There are HLA-A antigens that are immunogenically cross-reactive because they share determinant epitopes. CTL were not activated NK or LAK cells. The HLA restriction and melanoma cell specificity of the CTL were demonstrated by cold target inhibition with autologous and allogeneic melanoma and B lymphoblasts. Anti-CD3 and anti-HLA AB inhibited CTL killing of melanoma. The CTL were predominantly CD3+CD4+ TCR alpha/beta+. These studies demonstrate that melanomas being shared or cross-reactive HLA-A can be used for in vitro generation of HLA-restricted CTL that recognize melanoma-associated antigens. The findings have very important implications in human tumor immunotherapy.
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PMID:Induction of CD4+ cytotoxic T cells by sensitization with allogeneic melanomas bearing shared or cross-reactive HLA-A. 173 12

We compared the regulatory effects of interferon (IFN)-beta and IFN-gamma on the susceptibility of a human gliosarcoma line GI-1 to the attack of autologous cloned tumor-specific cytotoxic T-lymphocytes (CTL) and lymphokine-activated killer (LAK) cells. Preincubation of GI-1 cells with IFN-gamma caused augmented susceptibility to the cytotoxic attack of two autologous CTL clones, whereas IFN-beta exhibited no such marked effect. On the other hand, preincubation with either IFN-beta or IFN-gamma made the GI-1 cells resistant to the attack of autologous LAK cells. Both IFNs augmented the surface expression of HLA class-I molecules on GI-1 cells. A monoclonal anti-HLA class-I antibody blocked the cytolysis by one CTL clone, but not by the other one. These results suggest that IFN-gamma exerts some different effect (s) from that of IFN-beta on the target GI-1 cells in their susceptibility to the CTL-mediated cytolysis, and that recognition mechanisms of target cells by the CTL are different from those by LAK cells. This draws our attention to IFN administration in adoptive immunotherapy against brain tumors using CTLs and LAK cells.
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PMID:[Immunomodulatory effects of interferons on target human gliosarcoma cells in the tumor-specific CTL- and LAK-mediated cytolysis]. 176 55

The epidemiology of the 3 types of Kaposi's sarcoma, the endothelial tumor that occurs in classic, African, and immunosuppressed forms, associated pathological factors, potential causative agents, and a tentative model to explain the condition are contained in this review. Kaposi's sarcoma as classically described usually occurs in the lower limbs of elderly men, often from Mediterranean heritage, and progresses slowly. African Kaposi's sarcoma attacks the lymphatic system and viscera of all ages with a short survival time. Immunosuppressed people, especially AIDS sufferers, get a rapidly progressive but treatable form, that will regress if the immunosuppressive drug is withdrawn. Kaposi's sarcoma preceded the AIDS epidemic in the U.S., and it is apparently waning in AIDS patients. Factors linked to Kaposi's sarcoma include male gender, the HLA-DR5 genetic marker, abuse of nitrite drugs, exposure to semen or anal sex, or to several viruses. Cytomegalovirus is the most prominent of many viruses considered as a potential causal agent. Since many patients are free of CMV, it is now thought to be only a circumstantial factor because it is epidemic in Africa, is transmitted sexually, and causes immunosuppression. Several hypothetical models have been proposed to explain the phenomenon of Kaposi's, notably the multiple cofactor model, and the avian hemangiotosis retrovirus model, for an undiscovered sexually/enterically transmitted virus. It is possible that a single yet unknown agent, probably an oncogenic virus, with several routes of transmission, varying individual susceptibility, increased virulence for immune suppressed hosts, long latent period, and increasing endemicity is the infectious agent for Kaposi's sarcoma.
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PMID:The epidemiology of classic, African, and immunosuppressed Kaposi's sarcoma. 176 11

MHC class I antigens on tumor cells are expected to play an important role because they regulate the sensitivity to antitumoral immunological mechanisms. Overall or selective qualitative or quantitative changes in MHC molecules may modify the recognition of tumor cells by components of the immune system. It seems clear that MHC antigen expression on tumor cells is important in triggering the immune response by autologous lymphocytes. A deficiency in or lack of MHC class I antigens may have profound effects on T and NK cell activity. In experimental models, variation in the expression of MHC class I antigens has been shown to exert a decisive influence on local tumor growth and metastasis. However, there is little information about the influence of selective loss of individual locus products on the behavior of human tumor cells. Total and selective HLA losses have been found in a large variety of tumors, and different mechanisms have been shown to be responsible for these changes. In some examples, HLA losses are associated with a poor degree of tissue differentiation and poor prognosis. In other tumors, however, no such association has been found. We do not know whether HLA class II expression in neoplastic cells plays an immunological role, although, with the exception of melanoma, HLA class II expression is more frequently observed in tumors with a more favorable prognosis. Finally, there is no doubt that we need to learn more about how to manipulate the expression of MHC class I and II antigens in human tumors, in order to stimulate immune response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:MHC antigens on human tumors. 176 5

During the past 5 years, we have been conducting clinical trials with a therapeutic melanoma vaccine (melanoma "theraccine"). Mechanical lysates of two melanoma cell lines chosen for their complementary characteristics were combined with the adjuvant DETOX and injected subcutaneously on weeks 1, 2, 3, 4 and 6 for one or two courses, and then monthly in patients with objective clinical responses. Of 109 patients, 22 (20%) have had objective clinical regression of tumor masses, with 5% complete responses. Ten patients have lived more than a year. Eight of the 10 are still alive, five of whom have lived more than 3 years. It was not necessary to achieve complete remissions to cause an increase in survival, and most of the long-surviving patients have one or more (stable) residual nodules. The pace of the disease process has clearly been slowed in those individuals. A rise in the level of cytotoxic T lymphocyte precursors in the blood (pCTL) has correlated with clinical response. Only one patient without such a rise in pCTL has had a response, and assays in that patient were considered unreliable. Both CD4+ and CD8+ CTL have been cloned from the blood of immunized patients. Both types of CTL killed a number of melanoma cell lines, but not other types of tumor or normal cells (lymphoblasts and melanocytes). CD8+ CTL have not been restricted to killing the autologous melanoma. MHC restriction by the HLA-A2 locus was identified. CD4+ CTL were not restricted only by Class II HLA antigens. Many CD4+ clones killed HLA Class II-negative melanomas, and we were able to block cytotoxicity of a particular clone with either anti-HLA Class I or anti-Class II MHC monoclonal antibodies, or both. An association of clinical response to the theraccine with certain HLA phenotypes, notably HLA-C3, -A2 (and the cross-reactive HLA-A28), B12 (and the related alleles (HLA-B44 and -B45) and perhaps DR4, particularly when combinations of those alleles were present, was suggested by our analysis of 70 patients. It is possible that this simply indicates the sharing of MHC antigens between the immunizing melanomas and the patient's melanoma. However, these MHC molecules may be important in their own right in presenting melanoma-associated antigens in CTL in vivo. Subtractive hybridization of mRNA from lung squamous carcinoma cells from cDNA of the M-1 melanoma cell line has yielded several DNA sequences unique to melanoma. Those are now being analyzed for possible immunogenicity, with cytotoxicity by CTL from immunized patients as the major criterion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Attempts to optimize active specific immunotherapy for melanoma. 177 76


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