Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymphocyte clones were isolated from CD4+ peripheral-blood lymphocytes (PBL) of melanoma (Me) patient 9923 (HLA-DR7, DQw2, w6), co-cultured for 30 days with autologous accessory cells, allogeneic Me (Me 1811) (HLA-DR7, DQw1, w2), IL-1 beta (2 U/ml) and IL-2 (15 IU/ml). The 55 clones tested displayed a CD3+, CD4+, CD8-, T-cell receptor (TCR) alpha/beta+, gamma/delta- phenotype. Twenty clones were assayed for proliferation in the presence of Me 1811 and B-lymphoblastoid cell line (LCL) 1811, both expressing HLA-class-I and -II (DR7 and DQw2 shared with patient 9923), intercellular adhesion molecule-1 (ICAM-1) and lymphocyte-function-associated antigen-3 (LFA-3) molecules. Eight clones were found to be reactive to Me 1811 but not to LCL 1811. Specificity analysis of these 8 clones revealed that each of them proliferated only to Me 1811, not to other 14 Me and 12 different LCL, suggesting recognition of melanoma-associated antigen (MAA) expressed on the stimulating Me. One clone (103) was analyzed in more detail. A wider specificity analysis showed that it reacted to Me 1811 but not to 10 other Me expressing or not HLA-DR7, 5 normal melanocyte cultures (2 of them typing HLA-DR7-positive when exposed to interferon-gamma--IFN-gamma), 4 tumors other than Me and 20 different LCL. Clones did not show proliferation in the presence of autologous Me cells. Clone proliferation in response to Me 1811 was significantly inhibited by monoclonal antibodies (MAbs) directed to CD3, TCR alpha/beta, TCR beta chain V12, CD4 and HLA-DR. Moreover, following stimulation with Me 1811, clone 103 showed increased surface expression of CD25 (IL-2 receptor) and CD71 (transferrin receptor) and produced significant amounts of IL-2 and IFN-gamma. The supernatant taken from co-culture of clone 103 with Me 1811 augmented the cytotoxicity of PBL 9923 and other allogeneic PBL against K562 and Me 1811. Thus, the lymphocyte clone 103 is a CD4+ Th clone which uses its CD3/TCR alpha/beta complex to recognize an MAA in conjunction with HLA-DR7. Availability of this type of reagent may prove useful to identify and characterize MAA recognized by T lymphocytes.
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PMID:Human allogeneic melanoma-reactive T-helper lymphocyte clones: functional analysis of lymphocyte-melanoma interactions. 183 14

After a 5-day period of continuous intravenous infusion of recombinant interleukin 2 (rIL-2) in seven patients with malignant melanoma or gastric or pancreatic cancer, different lymphocyte subsets were separated from patients' blood and tested ex vivo for cytotoxic activity against various tumour cell lines. Lytic activity was mediated by CD3+CD56+, CD3-CD56+, CD3-CD2+ and CD8+CD56+ lymphocytes. No cytotoxic activity could be observed within the CD3+CD56-, CD3+CD2+ or CD4+ T cell subsets. To characterize CD56+ cytotoxic cells further, the expression of other antigens on this population was analysed before and after IL-2 therapy. CD3, CD4, CD16 and CD57 antigens were weakly expressed, and the IL-2 receptor (CD25) was not detectable on these cells either before and after treatment with IL-2. In contrast, increased expression of CD2. CD8 and HLA-DR antigens occurred following therapy. The divergence of CD3 and CD8 antigen expression after IL-2 therapy was caused by an increase in CD3-CD8+ cells, detectable as a low-density CD8+ subset. This study shows that cytotoxic activity of in vivo IL-2-activated killer cells is predominantly, but not exclusively, mediated by CD3-CD56+ lymphocytes, partially coexpressing the CD8 antigen and lacking the expression of CD16 antigens.
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PMID:Cytotoxic activity and phenotypic characteristics of lymphocyte subsets after therapy of cancer patients with interleukin-2. 187 92

Previous studies have suggested that, in human melanoma, expression of HLA-A2 antigen is important for tumor cell recognition by autologous T-lymphocytes. Because of the recent demonstration that expression of HLA Class I antigens may be selectively lost in several human tumors, including melanoma, we derived pairs of tumor infiltrating lymphocytes (TIL) and melanoma cell lines from 4 human lymphocytic antigen (HLA)-A2+ patients with metastatic melanoma. We observed that, although all 4 TIL cultures expressed HLA-A2 antigen, only 2 melanoma cell lines did so. Melanoma cells derived from the other 2 patients showed neither surface expression of the HLA-A2 antigen nor presence of the corresponding mRNA. We also observed some correlation between loss of HLA-A2 expression and level of c-myc transcription. TIL derived from patients whose melanoma cell lines had normal expression of HLA-A2 had a CD8 phenotype and were capable of lysing autologous melanoma cells. Melanoma cell killing was CD3 and major histocompatibility complex Class I restricted in both cases, but HLA-A2 restricted in only one case. On the other hand, TIL derived from the 2 patients whose melanoma cell lines had lost expression of HLA-A2 had a predominant CD4 phenotype and virtually no cytotoxic activity. Preincubation of the HLA-A2 negative melanoma cell lines with alpha- or gamma-interferon did not induce the re-expression of the HLA-A2 antigen. In an attempt to restore HLA-A2 antigen expression in one of the melanoma cell lines that were HLA-A2 negative, we transfected these cells with the HLA-A2 gene subcloned in the pSV2-neo vector. Four transfected clones, with high levels of HLA-A2 antigen expression, were expanded and characterized. Proliferative and cytotoxic activities of TIL against the autologous transfected clones as well as the untransfected parental melanoma cell line were measured and compared. CD4+ TIL showed no difference in the proliferative response to autologous parental and HLA-A2 transfected clones. However, we observed selective recognition of the HLA-A2 expressing clones by autologous cultured peripheral blood lymphocytes (which contained CD8 cells) as well as allogeneic CD8+ TIL with a HLA-A2 restricted pattern of recognition. In contrast, virtually no cytotoxic activity was detected against either parental or HLA-A2 transfected clones. Overall, our data suggest that selective down-regulation of HLA-A2 antigen expression in melanoma cells may represent one of the mechanisms by which tumor cells escape immunological recognition.
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PMID:Expression of HLA-A2 antigen in human melanoma cell lines and its role in T-cell recognition. 190 4

Cytotoxic T lymphocytes (CTL) specific for autologous human melanoma have been successfully generated in vitro from tumor bearing lymph nodes without any stimulation by the autologous tumor. Tumor-involved lymph node cells (LNC) were cultured in serum free medium (AIM-V) containing 1,000 U/ml of recombinant interleukin-2. The best expansion and specific cytotoxicity of CTL were achieved in 4 to 6 weeks of culture. The predominant populations in cultured LNC-derived CTL were CD2+, CD3+, CD4-, CD8+, CD56-, and HLA-DR+ T cells. These data suggested that tumor-involved LNC may provide an alternative source for the generation of tumor-specific CTL in adoptive immunotherapy.
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PMID:Generation of human autologous melanoma-specific cytotoxic T cells from tumor-involved lymph nodes. 191 Jun 25

This study was undertaken to investigate the effects of a single infusion of radiolabelled murine monoclonal antibody (MAb) on peripheral blood leukocytes in cancer patients. Eleven patients with disseminated colon cancer, malignant melanoma, or lung adenocarcinoma were infused with 111In-labelled anti-ZCE 025, anti-p97 type 96.5c, or LA 20207 MAb, respectively. Blood samples were obtained before infusion, immediately after infusion (1 hr), and at 4 and 7 days postinfusion. Flow cytometry analysis of CD3+, CD4+, CD8+, CD16+, and CD19+ lymphocytes showed increasing CD4:CD8 ratios in seven patients after infusion. This phenomenon was not restricted to antibody subclass or to type of cancer. Two of the remaining patients exhibited a marked post-infusion increase in CD8+ cells. In all three patients with malignant melanoma, decreasing levels of CD16+ lymphocytes were noted after infusion and natural killer cell cytotoxicity showed fluctuations which paralleled the changes in the CD16+ subpopulation. Oxygen radical production by phagocytic cells was markedly affected in three subjects. These results suggest that a single infusion of radiolabelled murine MAb may alter the balance of critical lymphocyte subpopulations and modulate other leukocyte responses in cancer patients.
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PMID:Effects of radiolabelled monoclonal antibody infusion on blood leukocytes in cancer patients. 196 68

To investigate the specificity of human tumor-infiltrating lymphocytes (TIL) against autologous tumors, TIL from five metastatic melanoma patients were expanded with rIL-2 and assessed for cytotoxicity in chromium release assays. TIL from a patient showing preferential cytotoxicity against autologous melanoma cells were further analysed. TIL were cloned by limiting dilution. Four out of 27 clones showed substantial cytotoxicity against autologous melanoma and one clone, designated as No. 8a-5 (CD3+, CD4-, CD8+, CD56-), selectively killed autologous melanoma but did not kill six different allogeneic melanoma, K562, or autologous or allogeneic Con A lymphoblast targets. Cytotoxicity of No. 8a-5 cells was inhibited by anti-HLA class I MAb (w6/32), by anti-beta 2-microglobulin MAb, and by anti-CD3 (OKT3) MAb, suggesting that the specific cytotoxicity was HLA class I-restricted and that the clone utilized the T-cell receptor complex for recognition of targets. Pretreatment with rIFN-gamma increased the sensitivity of autologous melanoma targets to lysis by No. 8a-5 cells. Exogenous rIL-4 enhanced [3H]TdR incorporation by these TIL. In contrast, rIFN-gamma reduced the sensitivity of the autologous melanoma to lysis by uncloned TIL, and rIL-4 suppressed the cytotoxicity and cell proliferation of uncloned TIL. These results indicate that both specific and non-specific cytotoxic cells can be developed from the same TIL and that these can be differentially regulated.
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PMID:Differential regulation by interleukin-4 and interferon-gamma of an autologous melanoma-specific cytotoxic T-cell clone and the tumor-infiltrating lymphocytes from which it was established. 211 66

In this study, we focused upon the immunologic aspects of Vogt-Koyanagi-Harada disease (VKH) by comparing the cytotoxic activity of peripheral blood leukocytes (PBL) to that of cerebrospinal fluid leukocytes (CSFL) against the human melanoma cell line (P-36) and the human cervical carcinoma cell line (HeLa-S3). The PBL from patients with VKH showed significant cytotoxic activity against P-36 (P less than 0.01), but did not show cytotoxic activity against HeLa-S3. The CSFL showed significantly weaker cytotoxic activity against P-36 compared to that of PBL (P less than 0.02). We also analyzed the cell membrane surface markers applying monoclonal antibodies on PBL and CSFL. The percentage of OKT8+ (CD8: T cytotoxic/suppressor lymphocytes) cells was significantly lower in CSFL than in PBL (P less than 0.05). There was a tendency toward a higher percentage of HLA-DR+ cells (B lymphocytes, monocytes, macrophages, and activated T lymphocytes) and a higher ratio of OKT4+/8+ cells (CD4/CD8: T helper/inducer lymphocytes/T cytotoxic/suppressor lymphocytes) in CSFL from patients with VKH than in their PBL (P less than 0.1).
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PMID:Immunologic analysis of cerebrospinal fluid lymphocytes in Vogt-Koyanagi-Harada disease. 214 46

We evaluated the immediate and long-term effects on immune function measures of a 6-week structure psychiatric group intervention for patients with malignant melanoma. Along with a reduction in levels of psychological distress and greater use of active coping methods, the following immune changes were seen at the 6-month assessment point in the intervention-group patients (n = 35) compared with controls (n = 26): significant increases in the percent of large granular lymphocytes (defined as CD57 with Leu-7) and natural killer (NK) cells (defined as CD16 with Leu-11 and CD56 with NKH1) along with indications of increase in NK cytotoxic activity; and a small decrease in the percent of CD4 (helper/inducer) T cells. At the 6-week follow-up point, the majority of these changes were not yet observable. The results indicate that a short-term psychiatric group intervention in patients with malignant melanoma with a good prognosis was associated with longer-term changes in affective state, coping, and the NK lymphoid cell system. Affective rather than coping measures showed some significant correlations with immune cell changes.
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PMID:A structured psychiatric intervention for cancer patients. II. Changes over time in immunological measures. 214 62

Tumor infiltrating (TIL) and peripheral blood lymphocytes (PBL) were isolated from 18 patients with non-small cell lung cancer undergoing radical surgery. Surface marker analysis revealed that TILs and PBLs mainly consisted of CD3+ T cells and that TILs generally displayed a lower CD4/CD8 ratio. Differences were found in the expression of CD25 (IL-2 receptor) and DR (MHC class II) antigens, which were increased in TILs, and in the percentage of CD16+ natural killer (NK) cells, which was reduced in TILs as compared to PBLs. Accordingly, the NK activity of TILs was lower than that of PBLs, whereas neither TILs nor PBLs expressed spontaneous cytolytic activity against fresh autologous tumor cells, melanoma cells and the "NK-resistant" A549 lung carcinoma cell line. After 4 days of culture in medium with recombinant-interleukin-2 (rIL-2), TILs and PBLs acquired cytolytic activity against all cell targets, but TILs expressed higher levels of cytotoxicity than autologous PBLs only in 3 patients out of 16 tested. More importantly, both TILs and PBLs displayed similar levels of cytotoxic activity against autologous tumor cells. TILs and PBLs from 8 patients were also analyzed by a limiting dilution microculture system. Cloning efficiency was remarkably lower in TILs, and surface marker analysis of T cell clones confirmed that an accumulation of CD8+ lymphocytes, which displayed cytolytic activity in a lectin-dependent assay, occurred at the tumor site. The non-MHC-restricted cytolytic activity of TIL- and PBL-derived T cell clones against K562, A549, and allogeneic melanoma cells and the cytolytic activity against autologous tumor cells showed no significant differences. Only 53% of TIL clones released IL-2 in response to PHA + TPA stimulation, whereas 68% of PBL-derived clones were IL-2 producers. Moreover, most PBL- and TIL-derived clones released tumor necrosis factor alpha in response to mitogen stimulation.
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PMID:Peripheral blood and tumor infiltrating lymphocytes in non-small cell lung cancer: analysis at the population and clonal level. 217 60

This investigation examined the effect of retinoic acid on tumor progression and immunological status of mice bearing the B16-F10 melanoma (previously selected for high lung-colonizing capacity). Tumor cells were implanted s.c. in syngeneic C57BL/6 mice, half of which were treated with beta-all trans retinoic acid (RA). Although RA failed to exhibit direct toxicity on this variant at the concentration used, the immunologic aberrations induced by the tumors were diminished by i.p. RA administration (at 45 micrograms twice/week for 3 weeks). In mice bearing B16-F10 tumors, tumor burdens were decreased from 2.9% of body weight to 1.6%. The mitogenic responses of splenic lymphocytes to concanavalin A (ConA) were increased in tumor-bearing mice following this RA treatment. The presence of these tumor cells decreased the absolute number of CD4- and CD8-positive splenic lymphocytes. Following RA treatment, the CD8-positive population was increased in tumor-bearing mice, while the CD4+ population was not significantly altered. Since previous studies indicated that plasma membrane fragments (or vesicles) could alter lymphocyte distributions and proliferative capacities, the in vitro shedding of membrane fragments from B16-F10 tumor cells was assayed and observed to be decreased after continuous treatment of cultures with 10(-6) M RA for 21 days. Membrane shedding from B16-F10 cells was inhibited by 48.5% following RA treatment. Based on these in vivo and in vitro results, we suggest that RA treatment may diminish tumor growth by decreasing tumor-induced immunosuppressive events.
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PMID:Effect of retinoic acid on tumor-mediated immunologic alterations in mice bearing a variant of the B16 melanoma. 224 92


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