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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HLA antigen expression, cell ploidy determined by DNA content with flow cytometry, and tumor metastasis were analysed and studied in 51 cases of human colorectal cancer samples. It was observed that the pattern of HLA expression and lymph node metastasis varied significantly when the cancer cells were categorized into distinct ploidies. For tetraploid cancer cells, the percentage of positive expression of class I and II antigens were all 90.0% with no detectable metastasis. On the contrary, the expression of class I and II antigens were as low as 13.3% and 40.0% with metastasis in 26.7% of the samples from diploid group. or 20.0% and 40.0% with a metastasis percentage of 60.0% for heteroploid group. The relevant patterns for triploidy and aneuploidy were between the above three groups. The significance of the unexpected low metastasis of the tetraploid cancer cells both in clinical prognosis and mechanism studies is further discussed.
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PMID:[Relationship among expression of HLA antigen, cell ploidy and metastasis in human colorectal cancer]. 139 54

T-cell-enriched lymphocyte populations derived from the malignant exudate of a patient with ovarian carcinoma were exposed to autologous tumor cells in the mixed lymphocyte-tumor-cell culture (MLTC) and propagated for 42 days. Proliferation of lymphocytes depended on exposures to autologous tumor cells and on the presence of IL-2. After 7 days, the MLTC-lymphocytes lysed K562 and the autologous tumor cells. The latter effect was not inhibited by monoclonal antibodies (MAbs) reactive with MHC class-I antigens or with CD3. After 7 restimulations, the culture was enriched in CD8+ cells (92%) and showed selective lytic activity against the autologous tumor. This function was inhibited by the alpha-class I or alpha-CD3 MAbs, and also by antibodies reactive with the HLA B locus or B5 allele products. The antibodies reactive with HLA A molecules had no such effect. It seems therefore that the function of the CTLs was restricted by HLA B5. Analysis of the TCR beta genes indicated clonal T-cell expansion in this culture. This MLTC was 1 of 21 initiated with 11 blood- and 10 tumor-derived lymphocyte (TIL) populations prepared from the malignant effusions of ovarian carcinoma patients. None of these ex-vivo lymphocytes lysed autologous tumor cells. In 17 MLTCs the lymphocytes did not proliferate, and in 3 cultures the proliferation was maintained only for 2-3 weeks. In 3 of 4 cultures auto-tumor cytotoxicity was induced.
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PMID:HLA-B5-restricted auto-tumor-specific cytotoxic T cells generated in mixed lymphocyte-tumor-cell culture. 139 29

Peripheral blood lymphocytes from 146 patients with metastatic melanoma undergoing interleukin 2 (IL-2)-based immunotherapy were characterized for HLA A, B, Cw, DR, DQw, and DRw specificities. Patients had been enrolled into sequential treatment protocols with either IL-2 alone (28) or in combination with tumor-infiltrating lymphocytes (TILs) (86), alpha-interferon (26), lymphokine-activated killer cells (16), radiation therapy (7), cyclophosphamide (3), tumor necrosis factor (1), and interleukin 4 (1) for a total of 168 courses of therapy. HLA phenotype was then correlated with response rate and toxicity to IL-2. We noted: (a) a significant difference in the frequency of A11 (20.5% versus 10.2%; P < 0.05) allele between melanoma patients and the North American Caucasian population; (b) a significantly higher frequency of A11 phenotype among responders (40.5%) than in the melanoma patient population (20.5%; P < 0.01), which was even more obvious among patients responding to TIL therapy (47.4% versus 22.1%; P < 0.05); within TIL patients, responders also had an increased frequency of A19 (42.1% versus 25.6%; P < 0.05); (c) a correlation between the number of TILs received and response rate (P < 0.005); and (d) an association between DR4 haplotype and decreased tolerance to IL-2 among the patients receiving TILs (P = 0.01). These results suggest that, in melanoma patients, some HLA Class I specificities may predict for a greater likelihood of response to IL-2-based therapy, while HLA Class II phenotype correlates with tolerance to the combination of TIL and IL-2 therapy.
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PMID:HLA association with response and toxicity in melanoma patients treated with interleukin 2-based immunotherapy. 142 1

Cytokine-induced modulation of HLA expression on the cell surface of four human breast cancer cell lines was determined by continuous flow immunocytofluorometry with the aid of monoclonal antibodies directed to a non-polymorphic determinant of HLA class I and class II (DR) antigen. IFN-gamma and IFN-alpha were potent inducers of HLA class I in all examined cell lines, with decreasing inducibility as follows: BT-20, ZR-75-1, MCF-7 and MDA-MB-468 cells. HLA class II (DR) antigen was highly inducible by IFN-gamma in ZR-75-1 cells, followed by BT-20, MDA-MB-468 and MCF-7 cells. IFN-alpha increased the cell surface expression of DR antigen only in ZR-75-1 cells. IL-1-alpha induced a moderate level of HLA class I antigen in ZR-75-1, BT-20 and MDA-MB-468 cells, and HLA class II (DR) expression only in ZR-75-1 cells. This pattern of cell line inducibility by IL-1-alpha was similar to that induced by TNF-alpha. Differences in inducibility of HLA antigens on human breast cancer cell lines induced by different cytokines may reflect the differences in cytokine inducibility of the original tumor cells.
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PMID:Cytokine (IFN-alpha, IFN-gamma, IL-1-alpha, TNF-alpha)-induced modulation of HLA cell surface expression in human breast cancer cell lines. 143 41

We have established that melanomas express shared tumor antigens (Ags) that can be recognized by T cells if presented in the context of self-MHC molecules. Tumor-infiltrating lymphocytes (TILs) from six melanoma patients were tested for lysis of large panels of HLA-matched or unmatched targets representing a variety of tissue types. Lysis was specific for allogeneic melanomas sharing at least one HLA-A, -B, or -C Ag with TILs, and demonstrated commonly expressed tumor Ags. Similar findings were obtained when cytokine secretion by TILs was used to indicate specific Ag recognition. Transfection of the HLA-A2.1 gene into HLA-A2- melanoma lines conferred susceptibility to lysis by HLA-A2 restricted melanoma TILs, demonstrating expression of common tumor Ags among patients of diverse HLA types. These findings have important implications for developing broadly applicable cancer immunotherapies such as vaccines.
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PMID:Recognition of shared melanoma antigens by human tumor-infiltrating lymphocytes. 144 13

Class II HLA antigen expression was investigated in biopsy material from patients with preclinical cervical carcinoma. Class II molecules were determined immunohistochemically by MoAb against HLA-DR antigens. A significant reduction of class II positive cells was established in the tumor tissue compared to the normal cervical epithelium. A correlation between the tumor progression and the inhibition of the class II antigen expression was found.
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PMID:Local immunosuppression determined by class II HLA antigen expression in patients with preclinical cervical carcinoma. 147 30

Immunophenotyping was conducted in 14 patients with malignant lymphoma of the skin using 4 monoclonal antibodies against CD4, 4, 8 and HLA (Ia--like) antigens. OKT4+ cells were detected in all the patients and OKT3+ cells in five of them. The expression of Ia-like antigen was noted in all patients with varying duration of the tumor process, in some of them Ia-like antigen prevailed that evidenced T-cell activation at all the stages of the tumor process in T-lymphomas of the skin. The highest expression of Ia-like antigen was recorded at the erythrodermal stage of granulomatosis of OKT4+ and OKT3+ phenotypes. Less pronounced expression of epidermal Ia-like tumor cells may be an evidence of a more benign course of the process.
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PMID:[Significance of Ia-like antigen expression in malignant lymphoma of the skin]. 147 22

Peripheral blood mononuclear cells obtained from 24 primary lung cancer patients were stimulated with anti-CD3 monoclonal antibody (alpha CD3MoAb) followed by culture with recombinant interleukin-2. The optimal concentration of alpha CD3MoAb for stimulation was 50 ng/ml in the liquid phase, and the sensitization culture was commenced at a cellular concentration of 1 x 10(6)/ml. Patients entered into this study were 14 cases of adenoca rcinoma, 7 of squamous cell carcinoma, and 3 of small cell carcinoma. After 4-6 days of stimulation with alpha CD3MoAb followed by culture with RIL-2 for 5-7 days, the cellular expansion was 3.7 folds (mean). Surface marker analysis of the cells revealed significant increments of CD3+, CD8+, HLA-DR+, and IL-2R+ cells after sensitization culture. In 2 cases, fresh autologous tumor cells could be obtained from surgical specimens. Effector cells generated in those 2 cases did not show significant cytotoxic activity against autologous tumor cells in 4 hr 51Cr release assay. In 5 cases, cytotoxicity against established lung cancer cell lines, STC-1 and L0301, were analyzed. In all cases, effector cells showed significant cytolytic activity against both targets. The sensitization culture utilizing alpha CD3MoAb was easy to perform and feasible for the majority of patients, and it is considered that utilization of this culture system would be worth while for adoptive immunotherapy in primary lung cancer patients.
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PMID:[Generation of effector cells from primary lung cancer patients by stimulation with anti-CD3 monoclonal antibody followed by culture with recombinant interleukin-2]. 148 32

The study of specific immunity in human cancers has been hampered by the elusive distribution and heterogeneity of effector cells. In this study, we have investigated the distribution of autologous melanoma-specific cytotoxic T lymphocytes (CTLs) in 18 different distant metastases from melanomas (9 non-visceral and 9 visceral metastases). Uncultured cells from tumors were provided directly for the establishment of T-cell clones using limiting dilution analysis to avoid any possible effects of in vitro sensitization of T cells to coexisting tumor cells. Autologous tumor specific CTL clones were detected in 6 of 18 tumors (33%, 4 non-visceral and 2 visceral metastases). The majority of CTL clones (35 of 46 and 17 of 19) in 2 patients with HLA class-I A2 haplotype failed to lyse either A2+ or A2- allogeneic melanoma cells, although anti-class-I (monomorphic) MAb inhibited their cytotoxicity. The remaining 11 of 46 and 2 of 19 CTL clones showed A2-restricted cytotoxicity. Autologous tumor-specific cytotoxicity was also detected after polyclonal culture of these tumor-infiltrating lymphocytes (TILs) in 8 of 16 tumors (50%, 5 non-visceral and 3 visceral metastases). These results suggest that tumor-specific T cells exist at tumor sites in at least one-third of distant metastases of melanomas and could be induced by the addition of IL-2 in at least half of the tumors. Tumor-specific T cells were detectable more often in non-visceral than in visceral metastases.
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PMID:Distribution of autologous tumor-specific cytotoxic T lymphocytes in human metastatic melanoma. 150 Feb 28

In our previous study, we found that serum beta 2-microglobulin (beta 2M) levels were elevated in the active, but not in the inactive, phase of adult T-cell leukemia (ATL), suggesting a correlation between the beta 2M level and the clinical severity of this disease. In this study we examined the mechanisms underlying the elevation of serum beta 2M levels in ATL. First, the production of beta 2M by ATL cells was investigated in vitro. High levels of beta 2M were detected in the conditioned culture medium (CM) of ATL cells from seven out of nine patients. Second, we assessed the effects of the CM on the release of beta 2M by three human cell lines unrelated to ATL (NCTC 2544, Chang liver, and L 132; originating from the skin, the liver, and the fetal lung, respectively). Most of the CM definitely promoted beta 2M production by these cell lines. beta 2M production by the cell lines was markedly promoted by exogenous interferon-gamma (IFN-gamma), a well-known potent inducer of class I HLA antigen expression. We then investigated whether an antibody directed against IFN-gamma could attenuate the activity of three ATL CM. The anti-IFN-gamma antibody reduced the stimulatory activity of the CM to 28-65% of the original level, but did not affect basal beta 2M production by these cell lines. These data suggest that there are at least two mechanisms causing the elevation of serum beta 2M levels in ATL; direct production by tumor cells, and production by non-malignant cells that is mediated via humoral factors secreted by the ATL cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Possible mechanisms for the elevation of serum beta 2-microglobulin levels in adult T-cell leukemia. 151 Nov 67


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