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)

We have analyzed the phenotypes of the T-cell subsets generated in response to Lewis lung carcinoma clones in C57BL/6J recipients. The metastatic derivative, which expresses low levels of H-2Kb gene, predominantly elicited CD8, V beta 8, and V beta 9+ T-cells. The nonmetastatic clone expressing high levels of H-Kb gene triggered a more heterogeneous response of V beta-5, -6, -8, -9, and -11 CD8+ T-cells. Comparison of the T-cell receptor (TCR) expression of the T-cells infiltrating the tumor site with the lymphocytes in the periphery of tumor-bearing animals revealed a pattern of homing of CD4+ T-cells bearing V beta-5, -6, and -11 TCR chains and CD8+ T-cells bearing V beta-5, -6, -9, and -11. Depletion of V beta 5 or V beta 6+ T-cells correlated with accelerated tumor growth, implying their protective role as tumor-specific effectors and consistent with the cytotoxicity of T-cells with this TCR phenotype. V beta 11 TCR expression in the tumor-infiltrating lymphocytes increased with the tumor size. Depletion of V beta 11+ T-cells enhanced resistance to primary tumor growth and conferred protection from metastasis in recipients cleared of V beta 5 and V beta 6 T-cell subsets. Those results suggest that tumor-specific effectors as well as negative regulator T-cells home, infiltrate, and coexist in the tumor site.
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PMID:T-cell subset analysis of Lewis lung carcinoma tumor rejection: heterogeneity of effectors and evidence for negative regulatory lymphocytes correlating with metastasis. 142 97

We have reported the establishment of two interleukin (IL)-2-dependent human leukemic cell lines (TALL-103/2 [CD3+TCR gamma delta +] and TALL-104 [CD3+ TCR alpha beta +]) which display major histocompatibility complex nonrestricted tumoricidal activity. Whereas TALL-103/2 cells lyse only natural killer cell-susceptible targets, TALL-104 cells display a broad range of tumor target reactivity. In reverse antibody-dependent cell-mediated cytotoxicity (ADCC), lysis by both cell lines is triggered by monoclonal antibodies (mAb) recognizing CD3 and, to a lesser extent, CD2, but not CD8 or CD56 antigens. In conventional cytotoxic assays, the lytic activity of both cell lines is strictly Ca(2+)-dependent. In reverse ADCC, lysis by TALL-103/2 cells is highly dependent on the presence of Ca2+, whereas TALL-104 cells seem to only partially require extracellular Ca2+. The cytoplasm of both cell lines contains azurophilic granules typical of cytotoxic cells. Northern blot analysis demonstrates mRNA expression of pore-forming protein (PFP; perforin) and serine esterases (SE). The magnitude of expression of these transcripts and of lytic activity depends on the doses of IL-2. Upon deprivation of IL-2, TALL-103/2 cells completely lose cytotoxic granules and function within 16 h, whereas TALL-104 cells progressively lose expression of PFP and SE mRNA, as well as killer activity, within 4 wk. Both anti-CD3 mAb and lysable target cells induce efficient BLT-esterase secretion from TALL-103/2 and TALL-104 cells analogous to findings with conventional cytotoxic T lymphocytes. The stable expression of tumoricidal activity over 2 yr in culture renders these cell lines unique and very useful for studies on the regulation of cell-mediated lysis in vitro and in animal models.
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PMID:Two unique human leukemic T-cell lines endowed with a stable cytotoxic function and a different spectrum of target reactivity analysis and modulation of their lytic mechanisms. 142 67

Phenotype of lymphocytes was estimated in 16 peritoneal fluids obtained from 9 ovarian cancer patients. Peritoneal fluids contained predominantly T cells (more than 80%) while B cell content was relatively low. Approximately 50% lymphocytes carried T-helper cell marker (CD4). Percentage of T-cytotoxic/suppressor cells (CD8+ cells) differed between patients with progression and those showing no tumor progression (19.0 +/- 7.5 vs 32.7 +/- 18.5). CD4/CD8 ratio was higher in the group of patients with progression than in the group with no progression of the tumor (3.4 +/- 2.1 and 2.0 +/- 1.5). Chemotherapy did not affect the parameters. Estimation of CD8 and CD4/CD8 ratio in peritoneal fluid cells could be helpful in monitoring of disease progression.
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PMID:Phenotype of lymphocyte in ovarian tumor peritoneal fluid. A preliminary study. 147 26

The phenotypic characteristics of freshly isolated tumor-infiltrating lymphocytes (TIL) obtained from human liver tumors were analyzed by two-color flow cytometry. TIL consisted of mainly CD3+ T-lymphocytes (70-80%). The ratio of CD4/CD8 in TIL from primary and metastatic liver tumors and autologous peripheral blood lymphocytes (A-PBL) was 1.3, 1.1 and 1.3, respectively. The majority of CD3+ T-lymphocytes (mean +/- SD; 95 +/- 11%) expressed T-cell antigen receptor (TCR) alpha/beta, and gamma/delta TCR positive T-cells were only 5 +/- 4.5% in TIL from both primary and metastatic liver tumors. TIL showed significantly higher percentages of transient activation markers, such as CD25 (Tac) and HLA-DR, than A-PBL. TIL also contained significantly more populations of CD3+ CD45RO+ T-lymphocytes, which are considered to be expressed on primed (memory) T-lymphocytes, than A-PBL. Furthermore, TIL from primary liver tumors demonstrated significantly higher percentages of CD3+ CD45RO+ T-cells than those from metastatic liver tumors. These data indicate that TIL from human liver tumors are an apparently distinct population from A-PBL, and that local immune responses against human primary and metastatic liver tumors might be different. Moreover, TIL from primary liver tumors consisted of mainly activated or primed (memory) T-cells, suggesting that they were sensitized and activated by autologous tumor cells in vivo. These observations may imply the possibility of adoptive immunotherapy using TIL against human primary liver tumors.
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PMID:Memory T-lymphocytes are the main population of tumor-infiltrating lymphocytes obtained from human primary liver tumors. 148 53

As unusual tumor-specific cytotoxic T lymphocyte (CTL) clone was isolated which expressed both CD4 and CD8 molecules. The target cells for this CTL can be induced to express either class I major histocompatibility complex (MHC) alone (with dimethylsulfoxide) or both class I and class II MHC (with interferon-gamma). Lysis of the tumor target depends on expression of class I MHC molecules, but does not require expression of class II MHC molecules. Furthermore, the lysis of target cells expressing both class I and class II is inhibited only by antibodies to class I (Kd), and not by antibodies to class II, demonstrating that the T cell receptor is class I restricted. We have used this CTL to assess the role of the interaction between CD4 and class II MHC in the absence of a class II-restricted T cell receptor. Our data indicate that CD4-class II interaction does not contribute to recognition by T cells in the absence of binding of the T cell receptor to class II molecules.
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PMID:CD4-class II major histocompatibility complex interaction does not enhance killing by a class I-restricted CD4+CD8+ cytotoxic T cell clone. 151 33

Peripheral blood lymphocytes (PBL) of gastric cancer patients in advanced stages showed lymphokine activated killer (LAK) activities comparable to those of healthy donors, suggesting potential applicability of LAK cells induced from PBL stimulated with recombinant interleukin-2 (rIL-2) in adoptive immunotherapy (AIT) for gastric cancer. In order to generate a large number of LAK cells from PBL, lymphocytes were cultured with both rIL-2 and phytohemagglutinin (PHA). In this culture, the numbers of cells increased to a greater extent than those in culture with rIL-2 alone but cytotoxic activity did not augment, thus suggesting that this procedure would not afford sufficient clinical effects. On the other hand, a large number of LAK cells with high anti-tumor activities were efficiently induced from spleen cells of the patients by culture of rIL-2; hence clinical usefulness of these LAK cells is anticipated. In regional lymph node lymphocytes (RLNL) cultured with rIL-2, the cytotoxic activities were lower than in those induced in PBL, and a characteristic increase of CD8 + CD11 + suppressor T cells was observed after incubation with rIL-2. Nevertheless, an increase of CD4 + 4B4 + helper inducer T cells was also observed in RLNL after the culture with rIL-2. Furthermore, high cytotoxic activities were induced in RLNL in some cases in which metastasis to the regional lymph nodes was not detected. When gastric cancer patients were pretreated with biological response modifiers (BRM), especially with Lentinan, LAK cells from PBL showed higher NK and LAK activities as compared with those of patients without BRM pretreatment.
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PMID:Evaluation of basic procedures for adoptive immunotherapy for gastric cancer. 152 56

Nineteen patients with metastatic liver tumor (9 of gastric cancer, 5 of colon cancer, 2 of pancreatic cancer, one each of mammary cancer, cholecystic cancer, carcinoid of biliary tract) and one patient with primary liver cancer were treated by endogenously induced LAK therapy consisting of transhepatic arterial infusion with ADM or MMC for induction therapy and OK-432 and rIL-2 (TGP-3) for immunotherapy. The following results were obtained. 1) Clinical response for liver tumor showed no CR but 8 cases of PR, for an overall response rate of 42.1%. 2) Reduced tumor marker value was noted in 76.5% cases, and 50% survival term became 349 days after the therapy. 3) Many CD4 and CD8 positive mononuclear cells had infiltrated around liver tumor after therapy by immuno-histochemical staining of surface marker. 4) NK activity of peripheral blood lymphocytes was markedly reduced soon after the therapy and continued for about 4-7 days, while in cases of combined subcutaneous administration with OK-432, NK activity showed only a slight decrease.
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PMID:[Significance of antitumor effects and immunological response on endogenously induced LAK therapy for primary or metastatic liver tumor]. 153 Feb 92

The effects of OK-432, a streptococcal preparation, administered intratumorally (OK-432 i.t.) on the change of lymphocyte subsets of regional lymph nodes were investigated in 26 gastric cancer patients. The results were as follows: 1) In the proximal lymph nodes, both non-metastatic and metastatic lymph nodes, and the proportion of CD3+ cells were slightly increased. 2) In the proximal lymph nodes without metastasis, the proportion of CD4+2H4+ cells and CD4+4B4- cells was increased about 10%. 3) In 4 of 15 patients who had metastatic lymph nodes macroscopic changes of the tumor and necrosis of metastatic lymph nodes by OK-432 i.t. were observed. In these lymph nodes CD8-CD11+ cells increased over 40%. These data suggested that the lymph node lymphocyte reaction by OK-432 i.t. may differ between metastatic lymph nodes and non-metastatic lymph nodes.
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PMID:[Effect of endoscopic local injection of OK-432 on regional lymph nodes in gastric cancer patients]. 153 Mar 16

Tumor-infiltrating lymphocytes (TIL) were isolated from a human melanoma metastatic to the abdomen. The TIL were 99% CD3+ and 99% CD4+ and CD8-. They were dependent on interleukin-2 (IL-2) for growth, as measured in a thymidine uptake assay, and were not cytotoxic to autologous or allogeneic melanoma or K562. When co-cultured with irradiated autologous tumor cells, or tumor cell supernatants, the TIL not only did not respond, but the IL-2-dependent growth was inhibited significantly. Inhibition occurred during the first 24 hours of co-culture and persisted as long as the tumor was present. After being washed free of inhibitory tumor cells, the TIL again were able to grow in the presence of IL-2, indicating that the inhibition was not caused by irreversible toxicity mediated by the tumor. Addition of excess IL-2 did not reverse the inhibitory effect, but addition of indomethacin, an inhibitor of cyclooxygenase and prostaglandin synthesis, partially blocked the inhibition. These data show melanoma-mediated inhibition of induction and expansion of human T-cells in vitro, which may reflect one of the mechanisms of inhibition of cellular responses in vivo. These results stress the need to examine the techniques for optimal in vitro expansion of tumor-specific TIL or cytotoxic T-cells for adoptive immunotherapy.
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PMID:Human melanoma-mediated inhibition of autologous CD4+ helper tumor-infiltrating lymphocyte growth in vitro. 153 42

Coculture of purified murine T cells with anti-CD3 monoclonal antibody (145-2C11) results in the induction of nonspecific cytotoxic T lymphocytes (CTL) with MHC-unrestricted cytolytic activity against a range of tumor targets. Serine proteases associated with effector cell granules are among the molecules postulated to play a role in cell-mediated cytolysis. The present study examines the ability of exogenous serine protease substrates to inhibit anti-CD3-activated cytotoxic T (ACT) cell-mediated killing of P815 mastocytoma and YAC1.2 lymphoma target cells. The chymotrypsin substrate N-acetyl-L-tyrosine ethyl ester (ATEE) was found to significantly inhibit ACT cell-mediated cytolysis. In contrast, the trypsin substrate N-benzoyl-L-arginine ethyl ester (BAEE) had little, if any, effect on ACT cell-mediated cytolysis. These effects were observed with both target cell populations. Conjugate inhibition studies performed with ATEE indicated that a chymotrypsin-like serine protease is involved in a postbinding event during cytolysis. Pretreatment of either target or effector cells with ATEE prior to cytolytic assay revealed that the chymotrypsin-like serine protease involved in cytotoxicity is of effector cell origin. Northern blot analysis of total RNA extracted from ACT cells revealed the presence of transcripts coding for CCP1 and CCP2 serine proteases known to be involved in antigen-specific CTL function, but little or no expression of the HF serine protease which has also been implicated in antigen-specific CTL killing. CCP2 exhibits chymotrypsin-like activity while HF displays trypsin-like activity. On the other hand, the CCP1 gene product has protease activity which resembles neither chymase nor tryptase activities. Thus, the level of mRNA expression for these serine proteases is consistent with our earlier observations, using the serine protease substrates, that a chymotrypsin-like serine protease but not a trypsin-like serine protease is involved in ACT cell-mediated cytolysis. "Lymphocyte panning" of ACT cells revealed abundant CCP1 and moderate CCP2 mRNA expression in CD4- and CD8+ anti-CD3-activated T cells with strong tumoricidal activity. CD8- anti-CD3-activated T cells with moderate cytolytic activity also expressed substantial levels of CCP1 and CCP2 mRNA, suggesting that both CD4- CD8- and CD4- CD8+ ACT cells participate in killing tumor targets. In contrast, CD4+ anti-CD3-activated T cells lacked both cytolytic activity and significant CCP1 and CCP2 mRNA expression. These findings are consistent with the involvement of chymotrypsin-like, as well as other, serine proteases in CTL-mediated lysis.
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PMID:Expression and utilization of chymotrypsin-like but not trypsin-like serine protease enzymes by nonspecific T killer cells activated by anti-CD3 monoclonal antibody. 153 39


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