1,721,169 research outputs found
The enigmatic role of interleukin-12 in the pathogenesis of Sjögren's syndrome: comment on the article by Vosters et al.
No full textVosters et al (1) recently reported that autoimmunityprone interleukin-12 (IL-12)–transgenic mice represent a new
model of Sjo ̈gren’s syndrome (SS) (1). IL-12–transgenic animals
were generated by expressing the biologically active IL-12 p70
heterodimer under the control of the thyroglobulin promoter.
The mice exhibited high serum levels of IL-12, and IL-12–
dependent lymphocytic infiltration of the thyroid, the lungs, and
the salivary and the lacrimal glands, mimicking human SS (2).
Vosters and colleagues demonstrated that salivary flow was
reduced in IL-12–transgenic mice compared with wild-type controls. Salivary glands showed increased lymphocytic infiltration
with reduced numbers of acini, and serum anti-SSB/La antibodies
(a serologic hallmark of SS [3]) were consistently detected,
together with antinuclear antibodies (ANAs)
Boosting natural killer cell-based immunotherapy with anticancer drugs. a perspective
No full textNatural killer (NK) cells efficiently recognize and kill tumor cells through several mechanisms including the expression of ligands for NK cell-activating receptors on target cells. Different clinical trials indicate that NK cell-based immunotherapy represents a promising antitumor treatment. However, tumors develop immune-evasion strategies, including downregulation of ligands for NK cell-activating receptors, that can negatively affect antitumor activity of NK cells, which either reside endogenously, or are adoptively transferred. Thus, restoration of the expression of NK cell-activating ligands on tumor cells represents a strategic therapeutic goal. As discussed here, various anticancer drugs can fulfill this task via different mechanisms. We envision that the combination of selected chemotherapeutic agents with NK cell adoptive transfer may represent a novel strategy for cancer immunotherapy. The well-established antitumor activity of NK cells is strictly dependent on the expression of ligands for NK cell-activating receptors on tumor cell surfaces. The molecular mechanisms underlying the upregulation of ligands for NK cell-activating receptors on tumor cells mainly depend on signaling pathways activated upon DNA damage induced by many different cytotoxic drugs. NK cell adoptive transfer in autologous or allogeneic settings represents a promising anticancer immunotherapeutic approach that has been tested in different clinical trials. The therapeutic efficacy of NK cell adoptive transfer may be dampened by downregulation of ligands for NK cell-activating receptors. A major immune-evasion mechanism adopted by most aggressive cancer cells. Many cytotoxic drugs utilized to treat cancer patients have been reported to upregulate the expression of ligands for NK cell-activating receptors in tumor cells, thus enhancing NK cell-mediated killing. Some of these drugs are excellent candidates for the design of new cancer immunotherapy protocols based on the combination of chemotherapy with allogeneic or autologous NK cell adoptive transfer
Enhancement of the in vitro colony-forming capacity of human T lymphocytes induced by levamisole.
No full textCytokines in neuroblastoma: From pathogenesis to treatment
No full textCytokines released by cancer cells or by cells of the tumor microenvironment stimulate angiogenesis, act as autocrine or paracrine growth factors for malignant cells, promote tumor cell migration and metastasis or create an immunosuppressive microenvironment. These tumor-promoting effects of cytokines also apply to neuroblastoma (NB), a pediatric neuroectodermal malignancy with frequent metastatic presentation at diagnosis and poor prognosis. IL-6 and VEGF are the best characterized cytokines that stimulated tumor growth and metastasis, while others such as IFN-? can exert anti-NB activity by inducing tumor cell apoptosis and inhibiting angiogenesis. On the other hand, cytokines are part of the anti-NB therapeutic armamentarium, as exemplified by IL-2 and granulocyte-macrophage colony stimulating factor that potentiate the activity of anti-NB antibodies. These recent results raise hope for more efficacious treatment of this ominous pediatric malignancy. © 2011 Future Medicine Ltd
Restoration of defective EAG-rosetting capacity of cancer patient neutrophils by levamisole.
No full textCancer associated fibroblasts in hematological malignancies
No full textTumor microenvironment plays an important role in cancer initiation and progression. In hematological malignancies, the bone marrow represents the paradigmatic anatomical site in which tumor microenvironment expresses its morphofunctional features. Among the cells participating in the composition of this microenvironment, cancer associated fibrobasts (CAFs) have received less attention in hematopoietic tumors compared to solid cancers. In this review article, we discuss the involvement of CAFs in progression of hematological malignancies and the potential targeting of CAFs in a therapeutic perspective
IL-17 superfamily cytokines modulate normal germinal center B cell migration
No full textThe germinal center (GC) is a dynamic structure formed by proliferating B cells in the follicles of secondary lymphoid organs during T cell-dependent antibody responses to exogenous antigens. GC is composed by a dark zone, enriched in proliferating centroblasts (CBs), and a light zone where CBs migrate and transform into centrocytes (CCs), a minority of which is selected to survive, undergoes Ig class-switch recombination, and differentiates into memory B cells or long-lived plasma cells. CBs express CXCR4 and are attracted to the dark zone by stromal cell-derived CXCL12, whereas CCs express CXCR5 and are recruited to the light zone along a gradient of CXCL13 produced by follicular dendritic cells (FDCs). Therefore, CXCL12 and CXCL13 play crucial roles in the regulation of GC B cell trafficking. Among the numerous molecules involved in GC formation, IL-17A represents a recent addition. Its involvement has been demonstrated in mouse models of human autoimmune or infectious diseases. IL-17A belongs to the IL-17 cytokine superfamily, together with 5 additional structurally related cytokines. We have recently demonstrated that IL-17A renders freshly isolated tonsil GC B cells competent to migrate to CXCL12 and CXCL13 through a NF-kBp65-dependentmechanism. Here, we review the role of IL-17A on GC cells and discuss, for the first time, common effects of the cognate cytokines IL-25 and IL-17B on GC B cell function. © Society for Leukocyte Biology
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