Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HLA-G is a non-classical MHC class I molecule whose suppressive activity on immune effector cells is exerted due to interactions with receptors ILT2, ILT4 and KIR2DL4. These receptors are expressed mainly on NK cells and monocytes, and their intensity of expression changes depending on HLA-G level. HLA-G plays an important role in the development of tolerance following organ transplantations and bone marrow stem cell transplantations. HLA-G also participates in the modulation of the immune response during cancerogenesis. The aim of this study was to assess HLA-G level in blood serum, the percentage of NK cells and monocytes with expression of receptors for HLA-G (ILT2, ILT4, KIR2DL4 and NKG2D) in patients who received allogeneic stem cell transplantations, and their influence on the occurrence of graft-versus-host reaction. The study included 32 patients with bone marrow diseases (acute leukemias, myelodysplastic syndrome, chronic myeloid leukemia, paroxysmal nocturnal hemoglobinuria) who received allogeneic stem cell transplantations. We assessed the expression of receptors ILT2, ILT4, KIR2DL4 and NKG2D on monocytes and NK cells, as well as the level of HLA-G in blood serum in patients before conditioning, in the transplant hematopoietic reconstitution period following allogeneic bone marrow stem cell transplantation. The percentage of NK cells with expression of KIR2DL4, ILT2 and ILT4 receptors was higher in patients with 0-I grade GVHD than in patients with II-IV grade GVHD. The percentage of monocytes with expression of ILT4 and ILT2 receptors was higher in patients with 0-I grade GVHD than in patients with II-IV grade GVHD. The level of HLA-G in patients' blood serum was higher after the stem cell transplantation compared with the period before transplantation. HLA-G level and HLA-G receptors are related to intensity of GVHD and may play the role of a prognostic factor for the development of GVHD and the clinical course of this reaction.
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PMID:The role of soluble HLA-G and HLA-G receptors in patients with hematological malignancies after allogeneic stem cell transplantation. 2618 79

Dendritic cells (DCs) play a crucial role in initiating and shaping immune responses. The effects of DCs on adaptive immune responses depend partly on functional specialization of distinct DC subsets, and partly on the activation state of DCs, which is largely dictated by environmental signals. Fully activated immunostimulatory DCs express high levels of costimulatory molecules, produce pro-inflammatory cytokines, and stimulate T cell proliferation, whereas tolerogenic DCs express low levels of costimulatory molecules, produce immunomodulatory cytokines and impair T cell proliferation. Relevant to the increasing use of immune checkpoint blockade in cancer treatment, signals generated from inhibitory checkpoint molecules on DC surface may also contribute to the inhibitory properties of tolerogenic DCs. Yet, our knowledge on the expression of inhibitory molecules on human DC subsets is fragmentary. Therefore, in this study, we investigated the expression of three immune checkpoints on peripheral blood DC subsets, in basal conditions and upon exposure to pro-inflammatory and anti-inflammatory stimuli, by using a flow cytometric panel that allows a direct comparison of the activatory/inhibitory phenotype of DC-lineage and inflammatory DC subsets. We demonstrated that functionally distinct DC subsets are characterized by differential expression of activatory and inhibitory molecules, and that cDC1s in particular are endowed with a unique immune checkpoint repertoire characterized by high TIM-3 expression, scarce PD-L1 expression and lack of ILT2. Notably, this unique cDC1 repertoire was subverted in a group of patients with myelodysplastic syndromes included in the study. Applied to the characterization of DCs in the tumor microenvironment, this panel has the potential to provide valuable information to be used for investigating the role of DC subsets in cancer, guiding DC-targeting treatments, and possibly identifying predictive biomarkers for clinical response to cancer immunotherapy.
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PMID:Costimulatory Molecules and Immune Checkpoints Are Differentially Expressed on Different Subsets of Dendritic Cells. 3124 60