Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adoptive immunotherapy is used to treat malignant tumors resistant to conventional therapeutic modalities. Patients with metastatic melanoma, renal cell carcinoma or mesothelioma are most likely to benefit from this treatment. Tumor infiltrating lymphocytes (TIL) contain tumor specific killer cells and are found to be the most effective. When TIL is not available or until it can be produced in sufficient amount, autologous activated lymphocytes (AAL) are an alternative. AAL are leukapheresed lymphocytes, activated by conditioned medium from OKT3 stimulated autologous lymphocytes. Subcutaneous IL-2 and oral cimetidine are also administered to support the reinfused AAL and to inhibit activation of CD8+ suppressor cells, respectively. To improve the yield and activation of reinfused lymphocytes, addition of IL-2 to the culture medium was tested in different time intervals after the onset of the culture. Interleukin-2 added in the first or second day i) improved the yield of activated lymphocytes; ii) increased the expression of activation markers CD25 (IL-2 receptor) and HLA-DR and iii) augmented killing of tumor cells. Later addition of IL-2 had no or negative effects. In vitro priming of peripheral blood mononuclear cells with autologous or allogeneic but histologically identical tumors was used to increase tumor-specificity of AAL. Autologous serum, containing antibodies specific to tumor cells, facilitated antigen presentation and yielded cytotoxic lymphocytes capable of efficiently killing tumor cells.
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PMID:Adoptive immunotherapy with activated peripheral blood lymphocytes. 815 78

This work was designed to study the proliferative response of tumor-associated lymphocytes (TAL) from neoplastic effusions against autologous tumor cells and the immunophenotype pattern of TAL from neoplastic effusions and that of PBMC of the same patients. We also compared the serum levels of the cytokines interleukin (IL) 1 beta, 2 and 6, tumor necrosis factor-alpha (TNF alpha) and soluble IL-2 receptor (sIL-2R) with those present in neoplastic effusions of the same patients. Moreover, we examined the ability of TAL and peripheral blood mononuclear cells (PBMC) to produce and release the cytokines and sIL-2R and to express membrane CD25 following their stimulation with phytohemagglutinin (PHA) in vitro. Finally, we compared the cytokines/sIL-2R production and membrane CD25 expression by PHA-stimulated PBMC of the patients with neoplastic effusions with a series of 90 cancer patients without neoplastic effusions and 20 normal healthy subjects. Thirteen neoplastic pleural and eight peritoneal effusions were collected from 11 patients with primary lung cancer, 7 with primary epithelial ovarian cancer, 1 with breast cancer, 1 with pleural mesothelioma, and 1 with pancreatic cancer. The proliferative response of TAL from neoplastic effusions against autologous tumor cells was lower than the response to PHA, IL-2, and anti-CD3, but significant. The percentage distribution of CD3+ and CD8+ lymphocyte subpopulations was higher in peritoneal than in pleural effusions, while the CD16+ subset was higher in pleural than in peritoneal effusions. The percentage distribution of CD16+ was significantly lower in pleural effusions than in PBMC of patients with pleural effusions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor-associated lymphocytes (TAL) are competent to produce higher levels of cytokines in neoplastic pleural and peritoneal effusions than those found in sera and are able to release into culture higher levels of IL-2 and IL-6 than those released by PBMC. 852 43

IL-18 is expressed in various reproductive organs and its expression in the uterus fluctuates in linkage with menstrual cycle, implantation, pregnancy and delivery. However, the roles of this cytokine in reproduction remain obscure. IL-18 is a pleiotropic cytokine and exerts apparently complicated and sometimes paradoxical functions in immune and inflammatory responses, and a consensus understanding of its action has not been attained. Recent investigations reveal that IL-18 activates anti-apoptotic signals and promotes both survival and proliferation of activated lymphocytes as well as various cells exposed to different stressors. Especially, IL-18 enhances the expansion of NK and gammadelta T cells isolated from the circulation and stimulated in various ways. The expansion of gammadelta T cells, stimulated by zoledronate and IL-2, was strongly promoted by exogenous IL-18 and was inhibited by neutralizing anti-IL-18 receptor antibody. The expansion of gammadelta T cells was coincident with an increased number of CD11c+ cells. The gammadelta T cells that expanded in the presence of zoledronate, IL-2 and IL-18 exhibited the phenotype of effector memory cells characterized as CD44+ CD27- CD45RA- cells. In addition, they expressed NKG2D, perforin, CD94, CD25 and CD122, and 30-40% of them were positive for CD56. Incubation of expanded gammadelta T cells with IL-18 induced production of GM-CSF, IFNgamma and TNFalpha at much higher levels than those incubated without IL-18. They showed strong cytotoxicity against tumor cells, including mesothelioma cells, and inhibited growth of mesothelioma xenografts in mice. These observations suggest that IL-18 can efficiently promote expansion of gammadelta T cells with potent cytotoxicity.
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PMID:Modulation of innate immunity by IL-18. 1985 8

Zoledronate (Zol) has recently been shown to expand gammadelta T cells that play important roles in host defenses against infection and tumors. In this study, we examined effects of interleukin-18 (IL-18) on expansion of gammadelta T cells in human peripheral blood mononuclear cells (PBMCs) stimulated by Zol and IL-2. The expansion of gammadelta T cells stimulated by Zol and IL-2 was strongly promoted by exogenous IL-18, and to the contrary, inhibited by neutralizing anti-IL-18 receptor antibody. The gammadelta T cells that expanded in the presence of Zol, IL-2, and IL-18 exhibited the phenotype of effector memory cells characterized by CD44 (+), CD27 (-), and CD45RA (-). In addition, they expressed NKG2D, perforin, CD94, CD25, and CD122, and 15% to 40% of them were positive for CD56. Incubation of gammadelta T cells in the presence with IL-18 produced GM-CSF, IFN-gamma, and TNF-alpha at much higher levels than those incubated without IL-18. They showed strong cytotoxicity against tumor cells including mesothelioma cells and inhibited growth of xenograft of mesothelioma in mice. These observations indicate that IL-18 can efficiently promote expansion of gammadelta T cells with potent antitumor activity.
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PMID:Effect of IL-18 on expansion of gammadelta T cells stimulated by zoledronate and IL-2. 2044 49