FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2988335909> ?p ?o ?g. }

• W2988335909 endingPage "3029" @default.
• W2988335909 startingPage "3029" @default.
• W2988335909 abstract "INTRODUCTION: CXCL9, CXCL10 and CXCL11 (CXCL9-10-11) are closely related cytokines that specifically bind to their receptor CXCR3. They act inducing chemotaxis, proliferation and/or cytotoxicity of CD4+ Th1 and cytotoxic T cells, which express CXCR3. Although the CXCL9-10-11/CXCR3 axis promotes immune activation, their pro- or anti-tumor effects in chronic lymphocytic leukemia (CLL) remain controversial. The aims of this study are: 1. To investigate serum levels of CXCL9-10-11 and the protein expression of their receptor CXCR3, as well as Th1 and cytotoxic gene expression signatures and protein expression of the cytotoxic molecules granzyme B and perforin in peripheral blood (PB) CD4+ T cells of controls, CLL-like monoclonal B-cell lymphocytosis (MBL) and CLL Binet stage A patients. 2. To assess the correlations between all previous parameters. 3. To evaluate Th1, cytotoxic and PD1+ T cell populations during disease progression. METHODS: Samples from 52 MBL subjects, 61 untreated CLL patients (Binet stage A/B [CLL-A/CLL-B]: 53/8) and 31 age-matched controls were employed. Serum levels (pg/mL) of CXCL9-10-11 were measured in 24 controls, 41 MBL and 44 CLL-A patients using Human CXCL9/MIG Quantikine ELISA Kit (R&D Systems) and U-PLEX Platform (Meso Scale Discovery). In addition, cryopreserved PB mononuclear cells from 8 controls, 11 MBL, 10 CLL-A and 8 CLL-B were studied by flow cytometry. Anti-CD3, anti-CD4, anti-granzyme B, anti-perforin, anti-CXCR3 and anti-PD1 antibodies, FVS510 and Fixation/Permeabilization Kit were used for cell staining (BD Biosciences). Protein expression of CXCR3, granzyme B, perforin and PD1 (measured as percentage of positive cells in PB CD4+ T cells) was assessed using FACSCanto II cytometer (BD Biosciences). In addition, purified CD4+ cells from PB (purity≥90%) were isolated by immunomagnetic methods (Miltenyi Biotec) to analyze gene expression in 9 controls, 13 MBL and 14 CLL-A patients. Extracted RNA (RIN>7) was hybridized to GeneChip Human Gene 2.0 ST arrays (Affymetrix). Differential gene expression was evaluated with linear models in R, and genes with P-value<0.05 and |FC|>1.5 were considered differentially expressed. Linear regression and Pearson correlations were calculated to evaluate the relationship between the different components of the CXCL9-10-11/CXCR3 axis (Figure 1). P-values<0.05 were considered significant. RESULTS: MBL subjects showed significantly increased CXCL9-10-11 serum levels as well as CXCR3 protein expression, Th1 and cytotoxic gene expression and perforin protein expression in CD4+ T cells compared to controls. A similar trend was obtained for CLL-A versus controls, although the differences for CXCL10 and cytotoxic proteins did not achieve statistical significance despite their increased levels (Table 1). CXCL9 and CXCL10 serum levels were significantly and strongly correlated with CXCR3 protein expression in CD4+ T cells (r=0.746, P-value=0.001 and r=0.716, P-value=0.002, respectively). Very strong positive and significant correlations were also detected between CXCR3 protein expression and Th1 gene expression in CD4+ T cells (correlation coefficients >0.8 for 6/7 genes). Significant positive correlations were also observed between CXCR3 protein expression and cytotoxic genes as well as granzyme B protein (Table 2). Protein expression of CXCR3 and cytotoxic molecules were similarly increased in the different stages of the disease. However, CLL-B patients displayed an increased percentage of CD4+ T cells expressing PD1 (around 7% in MBL and CLL-A versus 16% in CLL-B), although significance was not achieved (Table 1). CONCLUSIONS: 1. The increased levels of the different components of the CXCL9-10-11/CXCR3 axis in MBL and CLL-A, together with the strong correlations observed, point to an important activation of this molecular pathway in the first stages of the disease. 2. Correlations between CXCR3 and Th1/cytotoxic genes/proteins suggest that the increased Th1/cytotoxic features of CD4+ T cells in MBL and CLL-A are triggered by CXCL9-10-11/CXCR3 stimulation, and might be considered as a potential target for CLL immunotherapy. 3. The lower percentage of PD1+ CD4+ T cells in MBL/CLL-A may allow efficient effector Th1/cytotoxic responses at these stages of the disease. ACKNOWLEDGEMENTS. PI11/01621, PI15/00437, 2017/SGR437, Fundació La Caixa, Fundación Española de Hematología y Hemoterapia (FEHH). Disclosures Gimeno: Abbvie: Speakers Bureau; JANSSEN: Consultancy, Speakers Bureau. Rai:Genentech/Roche: Membership on an entity's Board of Directors or advisory committees; Pharmacyctics: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Cellectis: Membership on an entity's Board of Directors or advisory committees. Abrisqueta:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau; Abbvie: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau. Bosch:Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AstraZeneca: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau." @default.
• W2988335909 created "2019-11-22" @default.
• W2988335909 creator A5007117385 @default.
• W2988335909 creator A5014948608 @default.
• W2988335909 creator A5016547463 @default.
• W2988335909 creator A5020876694 @default.
• W2988335909 creator A5023726309 @default.
• W2988335909 creator A5023738506 @default.
• W2988335909 creator A5027401229 @default.
• W2988335909 creator A5036270463 @default.
• W2988335909 creator A5036625600 @default.
• W2988335909 creator A5039249480 @default.
• W2988335909 creator A5040500242 @default.
• W2988335909 creator A5052079364 @default.
• W2988335909 creator A5052838795 @default.
• W2988335909 creator A5054008156 @default.
• W2988335909 creator A5056009033 @default.
• W2988335909 creator A5058811742 @default.
• W2988335909 creator A5067708412 @default.
• W2988335909 creator A5081688805 @default.
• W2988335909 creator A5088137199 @default.
• W2988335909 date "2019-11-13" @default.
• W2988335909 modified "2023-10-18" @default.
• W2988335909 title "Deciphering the CXCL9-CXCL10-CXCL11/CXCR3 Axis in CLL-like Monoclonal B-Cell Lymphocytosis and Chronic Lymphocytic Leukemia: A New Target for Immune Activation?" @default.
• W2988335909 doi "https://doi.org/10.1182/blood-2019-122061" @default.
• W2988335909 hasPublicationYear "2019" @default.
• W2988335909 type Work @default.
• W2988335909 sameAs 2988335909 @default.
• W2988335909 citedByCount "0" @default.
• W2988335909 crossrefType "journal-article" @default.
• W2988335909 hasAuthorship W2988335909A5007117385 @default.
• W2988335909 hasAuthorship W2988335909A5014948608 @default.
• W2988335909 hasAuthorship W2988335909A5016547463 @default.
• W2988335909 hasAuthorship W2988335909A5020876694 @default.
• W2988335909 hasAuthorship W2988335909A5023726309 @default.
• W2988335909 hasAuthorship W2988335909A5023738506 @default.
• W2988335909 hasAuthorship W2988335909A5027401229 @default.
• W2988335909 hasAuthorship W2988335909A5036270463 @default.
• W2988335909 hasAuthorship W2988335909A5036625600 @default.
• W2988335909 hasAuthorship W2988335909A5039249480 @default.
• W2988335909 hasAuthorship W2988335909A5040500242 @default.
• W2988335909 hasAuthorship W2988335909A5052079364 @default.
• W2988335909 hasAuthorship W2988335909A5052838795 @default.
• W2988335909 hasAuthorship W2988335909A5054008156 @default.
• W2988335909 hasAuthorship W2988335909A5056009033 @default.
• W2988335909 hasAuthorship W2988335909A5058811742 @default.
• W2988335909 hasAuthorship W2988335909A5067708412 @default.
• W2988335909 hasAuthorship W2988335909A5081688805 @default.
• W2988335909 hasAuthorship W2988335909A5088137199 @default.
• W2988335909 hasConcept C13373296 @default.
• W2988335909 hasConcept C154317977 @default.
• W2988335909 hasConcept C167672396 @default.
• W2988335909 hasConcept C17502307 @default.
• W2988335909 hasConcept C183193105 @default.
• W2988335909 hasConcept C202751555 @default.
• W2988335909 hasConcept C203014093 @default.
• W2988335909 hasConcept C2776062744 @default.
• W2988335909 hasConcept C2776090121 @default.
• W2988335909 hasConcept C2777938653 @default.
• W2988335909 hasConcept C2778461978 @default.
• W2988335909 hasConcept C2780126324 @default.
• W2988335909 hasConcept C2780380082 @default.
• W2988335909 hasConcept C502942594 @default.
• W2988335909 hasConcept C55493867 @default.
• W2988335909 hasConcept C5858377 @default.
• W2988335909 hasConcept C86803240 @default.
• W2988335909 hasConcept C8891405 @default.
• W2988335909 hasConceptScore W2988335909C13373296 @default.
• W2988335909 hasConceptScore W2988335909C154317977 @default.
• W2988335909 hasConceptScore W2988335909C167672396 @default.
• W2988335909 hasConceptScore W2988335909C17502307 @default.
• W2988335909 hasConceptScore W2988335909C183193105 @default.
• W2988335909 hasConceptScore W2988335909C202751555 @default.
• W2988335909 hasConceptScore W2988335909C203014093 @default.
• W2988335909 hasConceptScore W2988335909C2776062744 @default.
• W2988335909 hasConceptScore W2988335909C2776090121 @default.
• W2988335909 hasConceptScore W2988335909C2777938653 @default.
• W2988335909 hasConceptScore W2988335909C2778461978 @default.
• W2988335909 hasConceptScore W2988335909C2780126324 @default.
• W2988335909 hasConceptScore W2988335909C2780380082 @default.
• W2988335909 hasConceptScore W2988335909C502942594 @default.
• W2988335909 hasConceptScore W2988335909C55493867 @default.
• W2988335909 hasConceptScore W2988335909C5858377 @default.
• W2988335909 hasConceptScore W2988335909C86803240 @default.
• W2988335909 hasConceptScore W2988335909C8891405 @default.
• W2988335909 hasIssue "Supplement_1" @default.
• W2988335909 hasLocation W29883359091 @default.
• W2988335909 hasOpenAccess W2988335909 @default.
• W2988335909 hasPrimaryLocation W29883359091 @default.
• W2988335909 hasRelatedWork W1969504080 @default.
• W2988335909 hasRelatedWork W1983122232 @default.
• W2988335909 hasRelatedWork W2017949628 @default.
• W2988335909 hasRelatedWork W2058581379 @default.
• W2988335909 hasRelatedWork W2119058768 @default.
• W2988335909 hasRelatedWork W2618779717 @default.
• W2988335909 hasRelatedWork W2988335909 @default.
• W2988335909 hasRelatedWork W4200379672 @default.
• W2988335909 hasRelatedWork W4286560817 @default.

• next