DOCSLIB.ORG

Serum Proteomic Analysis of Multiple Myeloma Subjects Treated with Daratumumab Monotherapy

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Serum Proteomic Analysis of Multiple Myeloma Subjects Treated with Daratumumab Monotherapy 1837 Serum Proteomic Analysis of Multiple Myeloma Subjects Treated With Daratumumab Monotherapy Tineke Casneuf, 1 Andrew Lysaght, 2 Clare LeFave, 3 Jaime Bald, 4 Brendan Weiss, 5 Niels W.C.J. van de Donk, 6 Henk M. Lokhorst, 6 Tahamtan Ahmadi, 4 A. Kate Sasser 4, * 1Janssen Research & Development, Beerse, Belgium; 2Immuneering Corporation, Cambridge, MA, USA; 3LabConnect, LLC, Seattle, WA, USA; 4Janssen Research & Development, LLC, Spring House, PA, USA; 5Division of Hematology/Oncology, Department of Medicine, Abramson Cancer Center and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 6Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands. *Presenting author. – Site ID was determined to be significantly associated with ✦ Expression of interleukin (IL)-1ß was significantly lower in – PD-L1/CD274 is the ligand for the receptor PD-1; the ✦ Two proteins, VCAM1 and GSN, were identified by all TLR2 ICOS CD163 INTRODUCTION METHODS the variables of interest (eg, demographics, response responders compared to non-responders ( P = 0.046; –7 engagement of PD-1 on T cells leads to reduced T-cell 3 applied statistical tests (shown in red text in Table 1 ) P = 0.001 14 P = 0.007 P = 2.53!10 11.0 17 class, and sample time point; ≥7.37% variability explained; Figure 4B ) 13.0 function and increased regulatory T-cell development Daratumumab Study Designs Wald test P = 3.71×10 –9 ), and ComBat 7 was utilized to Table 1. Proteins Exhibiting Differential Expression – In the bone marrow microenvironment, high 13 12.5 correct for site ID effects to reduce the impact of site- n 10.5 PD-L1 Between Baseline Versus On-Treatment Samples by o i ✦ Daratumumab is a first-in-class, human anti-CD38 IgG1 ✦ GEN501 was a phase 1/2, open-label, multicenter study concentrations of IL-1ß elicit the release of IL-6, which s related effects within the data s 12.0 Statistical Test e 14 r 12 Responders Non-responders monoclonal antibody in clinical development across the conducted in 2 parts ( Figure 3 ) promotes myeloma cell survival and expansion p x multiple myeloma (MM) disease spectrum ✦ For GEN501 Part 2, paired baseline and on-study samples E 10.0 11.5 ● Wilcoxon ANOVA:Visit Friedman – Part 1 was a dose-escalation phase ✦ E-cadherin (CDH1) and P-cadherin (CDH3) were shown to 14 from 16 patients were run in 1 batch and the data were VCAM1 VCAM1 VCAM1 1,2 11 11.0 ✦ High levels of CD38 are expressed on myeloma cells be increased in responders ( P = 0.007 and 0.012, GSN GSN GSN – Part 2 was a dose-expansion phase pre-processed with the SomaLogic standardization 9.5 ● ● respectively; Figure 4B ) 10.5 ● CXCL12 THBS4 CXCL12 ✦ The antimyeloma activity of daratumumab is mediated workflow 13 ● ● IGHM MMP3 Baseline On BaselineOn Baseline On ● ● ● ✦ SIRIUS was a phase 2, open-label, international, multicenter ● treatment treatment treatment ● ● through a number of mechanisms of action, including – Soluble serum E-cadherin is an independent prognostic PRTN3 ● study of Simon 2-stage design ( Figure 3 ) ● ● ● n ● ● ● PLG Non-responder Responder Stable o complement-dependent cytotoxicity, antibody-dependent Statistical Analyses marker of poor survival for newly diagnosed patients i ● ● s ● s ● 12 ● THBS4 15 e ● cell-mediated toxicity, antibody-dependent cellular with MM r p ● ✦ Responders versus non-responders ● ● x MMP3 TLR2, toll-like receptor 2; ICOS, inducible T-cell co-stimulator; CD163, cluster of differentiation 163. ● 3,4 E ● ● ● phagocytosis, and apoptosis via cross-linking GEN501 SIRIUS ● ● 16 ● PIGR – The role of CDH3 is similar to that of CDH1 ● ● – Statistical comparison of protein concentration ● ● ● ● Boldface and underlined text indicates that the SOMAmer was also identified in the comparison of Figure 5. Immune-related proteins increased on ● ● ● 11 ● ● ✦ Two studies, GEN501 (ClinicalTrials.gov Identifier: Dose-escalation Randomization ● ● baseline versus on-treatment samples in SIRIUS. distributions in daratumumab responders (partial ● ● ● treatment in all response classes. ● VCAM1, vascular cell adhesion molecule 1; GSN, gelsolin; CXCL12, C-X-C motif chemokine 12; ● ● NCT00574288) and SIRIUS (NCT01985126), demonstrated A. ● IGHM, immunoglobulin heavy constant mu; PRTN3, proteinase 3; PLG, plasminogen; Color key ● ● response [PR], very good PR [VGPR], complete response ● ● THBS4, thrombospondin 4; MMP3, matrix metalloproteinase 3; PIGR, polymeric immunoglobulin and histogram ● that single-agent daratumumab had a tolerable safety ● receptor. Dose from 0.005-24 mg/kg 0 16 mg/kg 8 mg/kg [CR], and stringent CR [sCR]) versus non-responders 6 ● (n = 32) 10 0 (n = 16) (n = 18) t Differential Protein Changes in Responders Versus 4 profile and promising efficacy in patients with relapsed or n u ● (progressed disease [PD]) was performed at both baseline o 0 C refractory MM ( Figure 1 )5,6 2 Non-responders Due to Treatment and on treatment using 2 complementary methods: 0 Baseline On treatment Baseline On treatment Safety and response −4 −2 0 2 4 8 Row Z−Score ✦ 60 proteins were identified as having significantly evaluated Response evaluated (i) Wilcoxon rank-sum test on each individual SOMAmer Red lines indicate a decrease over time. Green lines indicate an increase over time. CONCLUSIONS 9 differential levels between responders and non-responders and (ii) Limma analysis on all SOMAmers simultaneously DYRK3 HMGB1 PD-L1, programmed cell death ligand 1. 40 PPIB An additional FLT3 ADAMTS13 upon daratumumab treatment CD163 35 TPM2 Dose-expansion 90 patients TNFSF8 – All P values were adjusted using the Benjamini-Hochberg CADM1 Figure 7. Changes in immune checkpoint marker PD-L1. ✦ Several proteins with differential expression CDC42BPB enrolled at DDR2 30 CAMK1 ENTPD5 ✦ Some of these proteins have known roles in myeloma DARA 16 mg/kg 10,11 MRC1 (BH) method for multiple hypothesis correction MST1 between responders and non-responders at baseline 25 BMP10 ADCYAP1 % TLR4.LY96 , biology (B-cell maturation antigen [BCMA], signaling IL1B 16 mg/kg 8 mg/kg 16 mg/kg CCL11 R were identified, many of which are associated with 20 KYNU GEN501 Part 2 CD84 R (n = 42) (n = 30) (n = 106) – Wilcoxon-adjusted P values are reported here CLEC7A HSD17B1 lymphocyte activation molecule [SLAM] family member 7 O 15 SIGLEC7 MM or CD38 HAPLN1 PSMA2 CSNK2A1 ✦ As in SIRIUS, treatment induced differential protein DNAJC19 [SLAMF7], transmembrane activator and CAML interactor 10 TNFRSF11A DARA, daratumumab. ✦ Baseline versus on treatment ING1 SHH CDC37 expression in GEN501 Part 2 ( Table 1 ) 5 IL11 [TACI], and beta-2-microglobulin [B2M]; Figure 6 ) ✦ 142 proteins were identified as differentially CNTF PES1 TNFSF9 0 CCL8 Figure 3. Study design for GEN501 and SIRIUS. – Baseline versus on treatment protein levels were TGM3 expressed between baseline and on treatment SOD2 CDH3 – Of the proteins identified, all but 3 were also identified in 8 mg/kg 16 mg/kg 8 mg/kg 16 mg/kg EGFR SERPINC1 MAP2K4 Immune and T-cell–related Proteins compared using 3 alternative statistical methods: (i) 2-way SERPINA4 GEN501 SIRIUS CDH1 NOTCH1 the comparison of baseline versus on-treatment samples – Two proteins involved in T-cell stimulation (TLR2 SEMA6A 12 SPARCL1 ✦ In both studies, patients were ≥18 years of age, had repeated-measures analysis of variance (ANOVA), (ii) the SET ✦ On treatment, expression of immune checkpoint marker HFE2 PDGFRB in SIRIUS PR VGPR CR sCR SLAMF7 and ICOS) increased in all patients 8 8 CFP R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R documented myeloma requiring systemic therapy, and Wilcoxon signed-rank test, and (iii) the Friedman test R programmed cell death ligand 1 (PD-L1) decreased in N N N N N N N N N N N N N N N N N had an Eastern Cooperative Oncology Group performance responders and increased in non-responders compared to – These results further validate the observations in the ✦ 60 proteins were identified as differentially ORR, overall response rate; PR, partial response; VGPR, very good partial response; CR, complete – All P values were adjusted to control false discovery rate Centered and scaled protein concentrations are presented in the rows, and patients are presented response; sCR, stringent complete response. status of ≤2 in the columns. The horizontal color-bar located above the heat map indicates response class: baseline ( Figure 7 ) SIRIUS study expressed between daratumumab responders using the BH method for multiple hypothesis correction purple = non-responder, green = responder. Figure 1. Overall response rates with daratumumab versus non-responders over time; these proteins – In GEN501, patients had relapsed from or were refractory monotherapy in GEN501 and SIRIUS. – A 2-way repeated-measures ANOVA 12 was applied to B. include markers of tumor burden, which decrease in to ≥2 prior lines of therapy, including proteasome MST1 TNFSF8 TNFSF9 BCMA SLAMF7 determine if significant time-point:response-class 8.75 Responders Non-responders Responders Non-responders responders and increase in non-responders inhibitors (PIs), immunomodulatory drugs (IMiDs), P = 0.012 P = 0.003 P = 0.019 ● ● ● interaction occurred for each SOMAmer; a modified 13 12.0 ● ● SomaLogic Platform ● chemotherapy, and autologous stem cell transplantation ● ✦ On treatment, PD-L1 expression decreased in ● 18 ● 8.50 ● ● ● Wilcoxon rank-sum test was applied as a post hoc test to ● ● ● ● ● ● ● ● ● ● ● n ● responders and increased in non-responders ● ● ● ● ● ● ✦ The SOMAscan Assay (SomaLogic, Inc., Boulder,
Load more

Recommended publications
  • Type I Interferons and the Development of Impaired Vascular Function and Repair in Human and Murine Lupus
    Type I Interferons and the Development of Impaired Vascular Function and Repair in Human and Murine Lupus by Seth G Thacker A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Immunology) in The University of Michigan 2011 Doctoral Committee: Associate Professor Mariana J. Kaplan, Chair Professor David A. Fox Professor Alisa E. Koch Professor Matthias Kretzler Professor Nicholas W. Lukacs Associate Professor Daniel T. Eitzman © Seth G Thacker 2011 Sharon, this work is dedicated to you. This achievement is as much yours as it is mine. Your support through all six years of this Ph.D. process has been incredible. You put up with my countless miscalculations on when I would finish experiments, and still managed to make me and our kids feel loved and special. Without you this would have no meaning. Sharon, you are the safe harbor in my life. ii Acknowledgments I have been exceptionally fortunate in my time here at the University of Michigan. I have been able to interact with so many supportive people over the years. I would like to express my thanks and admiration for my mentor. Mariana has taught me so much about writing, experimental design and being a successful scientist in general. I could never have made it here without her help. I would also like to thank Mike Denny. He had a hand in the beginning of all of my projects in one way or another, and was always quick and eager to help in whatever way he could. He really made my first year in the lab successful.
    [Show full text]
  • Mechanical Forces Induce an Asthma Gene Signature in Healthy Airway Epithelial Cells Ayşe Kılıç1,10, Asher Ameli1,2,10, Jin-Ah Park3,10, Alvin T
    www.nature.com/scientificreports OPEN Mechanical forces induce an asthma gene signature in healthy airway epithelial cells Ayşe Kılıç1,10, Asher Ameli1,2,10, Jin-Ah Park3,10, Alvin T. Kho4, Kelan Tantisira1, Marc Santolini 1,5, Feixiong Cheng6,7,8, Jennifer A. Mitchel3, Maureen McGill3, Michael J. O’Sullivan3, Margherita De Marzio1,3, Amitabh Sharma1, Scott H. Randell9, Jefrey M. Drazen3, Jefrey J. Fredberg3 & Scott T. Weiss1,3* Bronchospasm compresses the bronchial epithelium, and this compressive stress has been implicated in asthma pathogenesis. However, the molecular mechanisms by which this compressive stress alters pathways relevant to disease are not well understood. Using air-liquid interface cultures of primary human bronchial epithelial cells derived from non-asthmatic donors and asthmatic donors, we applied a compressive stress and then used a network approach to map resulting changes in the molecular interactome. In cells from non-asthmatic donors, compression by itself was sufcient to induce infammatory, late repair, and fbrotic pathways. Remarkably, this molecular profle of non-asthmatic cells after compression recapitulated the profle of asthmatic cells before compression. Together, these results show that even in the absence of any infammatory stimulus, mechanical compression alone is sufcient to induce an asthma-like molecular signature. Bronchial epithelial cells (BECs) form a physical barrier that protects pulmonary airways from inhaled irritants and invading pathogens1,2. Moreover, environmental stimuli such as allergens, pollutants and viruses can induce constriction of the airways3 and thereby expose the bronchial epithelium to compressive mechanical stress. In BECs, this compressive stress induces structural, biophysical, as well as molecular changes4,5, that interact with nearby mesenchyme6 to cause epithelial layer unjamming1, shedding of soluble factors, production of matrix proteins, and activation matrix modifying enzymes, which then act to coordinate infammatory and remodeling processes4,7–10.
    [Show full text]
  • Mechanism of Action Through an IFN Type I-Independent Responses To
    Downloaded from http://www.jimmunol.org/ by guest on September 25, 2021 is online at: average * The Journal of Immunology , 12 of which you can access for free at: 2012; 188:3088-3098; Prepublished online 20 from submission to initial decision 4 weeks from acceptance to publication February 2012; doi: 10.4049/jimmunol.1101764 http://www.jimmunol.org/content/188/7/3088 MF59 and Pam3CSK4 Boost Adaptive Responses to Influenza Subunit Vaccine through an IFN Type I-Independent Mechanism of Action Elena Caproni, Elaine Tritto, Mario Cortese, Alessandro Muzzi, Flaviana Mosca, Elisabetta Monaci, Barbara Baudner, Anja Seubert and Ennio De Gregorio J Immunol cites 33 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription http://www.jimmunol.org/content/suppl/2012/02/21/jimmunol.110176 4.DC1 This article http://www.jimmunol.org/content/188/7/3088.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2012 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767
    [Show full text]
  • IFN-Ε Protects Primary Macrophages Against HIV Infection
    RESEARCH ARTICLE IFN-ε protects primary macrophages against HIV infection Carley Tasker,1 Selvakumar Subbian,2 Pan Gao,3 Jennifer Couret,1 Carly Levine,2 Saleena Ghanny,1 Patricia Soteropoulos,1 Xilin Zhao,1,2 Nathaniel Landau,4 Wuyuan Lu,3 and Theresa L. Chang1,2 1Department of Microbiology, Biochemistry and Molecular Genetics and 2Public Health Research Institute, Rutgers University, New Jersey Medical School, Newark, New Jersey, USA.3Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, USA.4Department of Microbiology, New York University School of Medicine, New York, New York, USA. IFN-ε is a unique type I IFN that is not induced by pattern recognition response elements. IFN-ε is constitutively expressed in mucosal tissues, including the female genital mucosa. Although the direct antiviral activity of IFN-ε was thought to be weak compared with IFN-α, IFN-ε controls Chlamydia muridarum and herpes simplex virus 2 in mice, possibly through modulation of immune response. We show here that IFN-ε induces an antiviral state in human macrophages that blocks HIV-1 replication. IFN-ε had little or no protective effect in activated CD4+ T cells or transformed cell lines unless activated CD4+ T cells were infected with replication-competent HIV-1 at a low MOI. The block to HIV infection of macrophages was maximal after 24 hours of treatment and was reversible. IFN-ε acted on early stages of the HIV life cycle, including viral entry, reverse transcription, and nuclear import. The protection did not appear to operate through known type I IFN-induced HIV host restriction factors, such as APOBEC3A and SAMHD1.
    [Show full text]
  • CD95 Ligand - Death Factor and Costimulatory Molecule?
    Cell Death and Differentiation (2003) 10, 1215–1225 & 2003 Nature Publishing Group All rights reserved 1350-9047/03 $25.00 www.nature.com/cdd Review CD95 ligand - death factor and costimulatory molecule? O Janssen*,1, J Qian1, A Linkermann1 and D Kabelitz1 Tissue and Cellular Expression of CD95L 1 Institute for Immunology, Medical Center Schleswig-Holstein, Campus Kiel, Michaelisstrasse 5, D-24105 Kiel, Germany The CD95 ligand (CD95L, Apo-1L, FasL, CD178) is a 281- * Corresponding author: O Janssen. Tel: þ 49-431-5973377; Fax: þ 49-431- amino-acid-containing type II transmembrane protein of the 5973335; E-mail: [email protected] TNF family of death factors (Figure 1).1 Its death-inducing function is best documented in the context of activation- Received 24.4.03; revised 12.6.03; accepted 20.6.03; published online 1 August 2003 induced cell death (AICD) in T cells.2 CD95L is expressed as a Edited by T Ferguson death factor in cytotoxic T lymphocytes (CTL) to kill virally infected or transformed target cells and in natural killer (NK) cells, where it is upregulated by CD16 engagement and 3 Abstract cytokines including IL-2 and IL-12. Similarly, high levels of intracellular CD95L have been detected in monocytic cells The CD95 ligand is involved as a death factor in the with an inducible release upon activation.4 Under physiologi- regulation of activation-induced cell death, establishment cal conditions, CD95L is implicated in the control of erythroid of immune privilege and tumor cell survival. In addition, differentiation,5 angiogenesis in the eye6 and skin home- 7 CD95L may serve as a costimulatory molecule for T-cell ostasis.
    [Show full text]
  • Development and Validation of a Protein-Based Risk Score for Cardiovascular Outcomes Among Patients with Stable Coronary Heart Disease
    Supplementary Online Content Ganz P, Heidecker B, Hveem K, et al. Development and validation of a protein-based risk score for cardiovascular outcomes among patients with stable coronary heart disease. JAMA. doi: 10.1001/jama.2016.5951 eTable 1. List of 1130 Proteins Measured by Somalogic’s Modified Aptamer-Based Proteomic Assay eTable 2. Coefficients for Weibull Recalibration Model Applied to 9-Protein Model eFigure 1. Median Protein Levels in Derivation and Validation Cohort eTable 3. Coefficients for the Recalibration Model Applied to Refit Framingham eFigure 2. Calibration Plots for the Refit Framingham Model eTable 4. List of 200 Proteins Associated With the Risk of MI, Stroke, Heart Failure, and Death eFigure 3. Hazard Ratios of Lasso Selected Proteins for Primary End Point of MI, Stroke, Heart Failure, and Death eFigure 4. 9-Protein Prognostic Model Hazard Ratios Adjusted for Framingham Variables eFigure 5. 9-Protein Risk Scores by Event Type This supplementary material has been provided by the authors to give readers additional information about their work. Downloaded From: https://jamanetwork.com/ on 10/02/2021 Supplemental Material Table of Contents 1 Study Design and Data Processing ......................................................................................................... 3 2 Table of 1130 Proteins Measured .......................................................................................................... 4 3 Variable Selection and Statistical Modeling ........................................................................................
    [Show full text]
  • Viewed by the Institutional Lab- M2mws Were Counted, and 1.03106 Viable Cells Were Suspended in Oratory Animal Care and Use Committee of Nagoya City University
    BASIC RESEARCH www.jasn.org Colony-Stimulating Factor-1 Signaling Suppresses Renal Crystal Formation † Kazumi Taguchi,* Atsushi Okada,* Hiroshi Kitamura, Takahiro Yasui,* Taku Naiki,* Shuzo Hamamoto,* Ryosuke Ando,* Kentaro Mizuno,* Noriyasu Kawai,* Keiichi Tozawa,* ‡ ‡ † Kenichi Asano, Masato Tanaka, Ichiro Miyoshi, and Kenjiro Kohri* Departments of *Nephro-urology, and †Comparative and Experimental Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; and ‡Laboratory of Immune Regulation, School of Science, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan ABSTRACT We recently reported evidence suggesting that migrating macrophages (Mws) eliminate renal crystals in hyperoxaluric mice. Mwscanbeinflammatory (M1) or anti-inflammatory (M2), and colony-stimulating factor-1 (CSF-1) mediates polarization to the M2Mw phenotype. M2Mws promote renal tissue repair and regeneration, but it is not clear whether these cells are involved in suppressing renal crystal formation. We investigated the role of M2Mws in renal crystal formation during hyperoxaluria using CSF-1–deficient mice, which lack M2Mws. Compared with wild-type mice, CSF-1–deficient mice had significantly higher amounts of renal calcium oxalate crystal deposition. Treatment with recombinant human CSF-1 increased the expression of M2-related genes and markedly decreased the number of renal crystals in both CSF-1– deficient and wild-type mice. Flow cytometry of sorted renal Mws showed that CSF-1 deficiency resulted in a smaller population of CD11b+F4/80+CD163+CD206hi cells, which represent M2-like Mws. Additionally, transfusion of M2Mws into CSF-1–deficient mice suppressed renal crystal deposition. In vitro phagocytosis assays with calcium oxalate monohydrate crystals showed a higher rate of crystal phagocytosis by M2- polarized Mws than M1-polarized Mws or renal tubular cells.
    [Show full text]
  • TNFSF9 Rabbit Polyclonal Antibody – AP20383PU-N | Origene
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for AP20383PU-N TNFSF9 Rabbit Polyclonal Antibody Product data: Product Type: Primary Antibodies Applications: IF, WB Recommended Dilution: Western Blot: 1/500-1/1000. Immunofluorescence: 1/50-1/200. Reactivity: Human, Mouse, Rat Host: Rabbit Clonality: Polyclonal Immunogen: Synthetic peptide, corresponding to amino acids 50-100 of Human 4-1BBL. Specificity: This antibody detects endogenous levels of 4-1BBL protein. (region surrounding Arg69) Formulation: PBS, pH 7.2 State: Aff - Purified State: Liquid purified Ig fraction (> 95% by SDS-PAGE) Preservative: 0.05% Sodium Azide Concentration: 1.0 mg/ml Purification: Immunoaffinity Chromatography Conjugation: Unconjugated Storage: Store undiluted at 2-8°C for one month or (in aliquots) at -20°C for longer. Avoid repeated freezing and thawing. Stability: Shelf life: one year from despatch. Predicted Protein Size: ~ 26 kDa Gene Name: Homo sapiens tumor necrosis factor superfamily member 9 (TNFSF9) Database Link: Entrez Gene 8744 Human P41273 This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 2 TNFSF9 Rabbit Polyclonal Antibody – AP20383PU-N Background: CD137, also designated ILA and 4-1BB in mouse, belongs to the tumor necrosis factor receptor family and delivers a costimulatory signal to T lymphocytes. CD137 is expressed on activated T cells and binds an inducible ligand that is found on B cells, macrophages and dendritic cells.
    [Show full text]
  • Myeloid Innate Immunity Mouse Vapril2018
    Official Symbol Accession Alias / Previous Symbol Official Full Name 2810417H13Rik NM_026515.2 p15(PAF), Pclaf RIKEN cDNA 2810417H13 gene 2900026A02Rik NM_172884.3 Gm449, LOC231620 RIKEN cDNA 2900026A02 gene Abcc8 NM_011510.3 SUR1, Sur, D930031B21Rik ATP-binding cassette, sub-family C (CFTR/MRP), member 8 Acad10 NM_028037.4 2410021P16Rik acyl-Coenzyme A dehydrogenase family, member 10 Acly NM_134037.2 A730098H14Rik ATP citrate lyase Acod1 NM_008392.1 Irg1 aconitate decarboxylase 1 Acot11 NM_025590.4 Thea, 2010309H15Rik, 1110020M10Rik,acyl-CoA Them1, thioesterase BFIT1 11 Acot3 NM_134246.3 PTE-Ia, Pte2a acyl-CoA thioesterase 3 Acox1 NM_015729.2 Acyl-CoA oxidase, AOX, D130055E20Rikacyl-Coenzyme A oxidase 1, palmitoyl Adam19 NM_009616.4 Mltnb a disintegrin and metallopeptidase domain 19 (meltrin beta) Adam8 NM_007403.2 CD156a, MS2, E430039A18Rik, CD156a disintegrin and metallopeptidase domain 8 Adamts1 NM_009621.4 ADAM-TS1, ADAMTS-1, METH-1, METH1a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 1 Adamts12 NM_175501.2 a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 12 Adamts14 NM_001081127.1 Adamts-14, TS14 a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 14 Adamts17 NM_001033877.4 AU023434 a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 17 Adamts2 NM_001277305.1 hPCPNI, ADAM-TS2, a disintegrin and ametalloproteinase disintegrin-like and with metallopeptidase thrombospondin
    [Show full text]
  • Genome Wide DNA Methylation Landscape Reveals Glioblastoma's Influence on Epigenetic Changes in Tumor Infiltrating CD4+ T
    www.oncotarget.com Oncotarget, 2021, Vol. 12, (No. 10), pp: 967-981 Research Paper Genome wide DNA methylation landscape reveals glioblastoma’s influence on epigenetic changes in tumor infiltrating CD4+ T cells Marpe Bam1,*, Sreenivasulu Chintala2,*, Kaleigh Fetcko2, Brooke Carmen Williamsen1, Seema Siraj1, Sheng Liu3, Jun Wan3, Xiaoling Xuei3, Yunlong Liu3, Adam T. Leibold2 and Mahua Dey1,2 1Department of Neurological Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA 2Department of Neurosurgery, Indiana University School of Medicine, Indianapolis, IN, USA 3Department of Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA *These authors contributed equally to this work Correspondence to: Mahua Dey, email: [email protected] Keywords: glioblastoma; malignant glioma; CD4+ T cell; DNA methylation; brain cancer Received: April 05, 2021 Accepted: April 19, 2021 Published: May 11, 2021 Copyright: © 2021 Bam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT CD4+ helper T (Th) cells play a critical role in shaping anti-tumor immunity by virtue of their ability to differentiate into multiple lineages in response to environmental cues. Various CD4+ lineages can orchestrate a broad range of effector activities during the initiation, expansion, and memory phase of endogenous anti-tumor immune response. In this clinical corelative study, we found that Glioblastoma (GBM) induces multi- and mixed-lineage immune response in the tumor microenvironment. Whole- genome bisulfite sequencing of tumor infiltrating and blood CD4+ T-cell from GBM patients showed 13571 differentially methylated regions and a distinct methylation pattern of methylation of tumor infiltrating CD4+ T-cells with significant inter- patient variability.
    [Show full text]
  • Inflammation-Related Plasma and CSF Biomarkers for Multiple Sclerosis
    Inflammation-related plasma and CSF biomarkers for multiple sclerosis Jesse Huanga, Mohsen Khademia, Lars Fuggerb,c, Örjan Lindhed, Lenka Novakovae, Markus Axelssone, Clas Malmeströme, Clara Constantinescue, Jan Lyckee, Fredrik Piehla, Tomas Olssona,1, and Ingrid Kockuma,1,2 aNeuroimmunology Unit, Center of Molecular Medicine, Department of Clinical Neuroscience, Karolinska University Hospital, Karolinska Institutet, SE-171 77 Stockholm, Sweden; bOxford Centre for Neuroinflammation, Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom; cNuffield Department of Clinical Neurosciences, Division of Clinical Neurology, University of Oxford, Oxford OX3 9DU, United Kingdom; dOlink Proteomics AB, SE-751 83 Uppsala, Sweden; and eDepartment of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden Edited by Tak W. Mak, University of Toronto, Toronto, ON, Canada, and approved April 10, 2020 (received for review July 26, 2019) Effective biomarkers for multiple sclerosis diagnosis, assessment bands are currently used to support diagnosis (10). In addition, of prognosis, and treatment responses, in particular those measur- there is a restricted set of CSF markers, including chemokine able in blood, are largely lacking. We have investigated a broad (C-X-C motif) ligand 13 (CXCL13), matrix metallopeptidase-9 set of protein biomarkers in cerebrospinal fluid (CSF) and plasma (MMP-9), and osteopontin (OPN), which have been associated using a highly sensitive proteomic immunoassay. Cases from two with inflammation, along with neurofilament light chains independent cohorts were compared with healthy controls and (NfL), a measure of neuron/axon damage (10–13).
    [Show full text]
  • PDF Attached
    ARTICLES Quantitative production of macrophages or neutrophils ex vivo using conditional Hoxb8 methods Gang G Wang1,2, Katherine R Calvo1,3, Martina P Pasillas1,DavidBSykes1,4, Hans Ha¨cker5 & Mark P Kamps1 Differentiation mechanisms and inflammatory functions of phagocyte functions, there is no simple protocol to generate large .com/nature e neutrophils and macrophages are usually studied by genetic and numbers of neutrophils or monocytes from these mutant mice to biochemical approaches that require costly breeding and characterize the impact of a genetic mutation on their differentia- .natur time-consuming purification to obtain phagocytes for functional tion, signal transduction or effector functions. w analysis. Because Hox oncoproteins enforce self-renewal of Class I Hox home domain transcription factors promote the factor-dependent myeloid progenitors, we queried whether expansion of hemopoietic progenitors, and their expression is estrogen-regulated Hoxb8 (ER-Hoxb8) could immortalize deregulated in both human and mouse myeloid leukemia. The http://ww macrophage or neutrophil progenitors that would execute normal abundance of Hoxa9 and Hoxa7 is high in CD34+, Sca-1+, lineage- differentiation and normal innate immune function upon negative (Lin–) bone marrow populations that are enriched in oup r G ER-Hoxb8 inactivation. Here we describe methods to derive hematopoietic stem cells (HSC) and in lineage-committed pro- unlimited quantities of mouse macrophages or neutrophils by genitors, and both are downregulated coincident with transition immortalizing their respective progenitors with ER-Hoxb8 using to the CD34– stage of early progenitor differentiation3,4. –/– lishing different cytokines to target expansion of different committed Hoxa9 mice have five- to tenfold fewer marrow HSC and b progenitors.
    [Show full text]