How does HBV interact with the immune system?
|
|
- Reginald Boyd
- 6 years ago
- Views:
Transcription
1 How does HBV interact with the immune system? International Workshop on HBV Cure Toronto 2017 Mala Maini Division of Infection and Immunity UCL
2 Disclosures Mala Maini: collaborative research funding from Gilead Sciences, Roche and Immunocore advisory boards and /or consultant for Gilead Sciences, Roche, Arbutus Biopharma
3 CD8 T cell depletion and dysfunction in persistent HBV? Acute resolving HBV Chronic HBV CD8 T cells Granzyme Perforin INF-g TNF-a IL-2 Infected hepatocytes Effective T cells control virus Infected hepatocytes Exhausted T cells loose control of virus
4 Restoration of endogenous T cells for functional cure Acute resolving HBV Chronic HBV CD8 T cells Granzyme Perforin INF-g TNF-a IL-2 Infected hepatocytes Effective T cells control virus Infected hepatocytes Exhausted T cells loose control of virus Feasible? Safe? How? In whom? Reviewed in Maini and Pallett, Lancet Gastro Hep in press
5 High antigen load and the liver environment drive T cell exhaustion in HBV Persistent high antigen load Infected hepatocytes + Defective particles fold excess over virions Tolerogenic liver environment Hepatocyte Blood from portal vein MAIT B cell CD4 NK CD8 T reg Space of Disse LSEC MDSC Kupffer cell Stellate cell
6 Multiple immune defects in HBV infection B cells skewed: IL-10-mediated T cell suppression Das JI 2012 B cell MAIT CD4 NK CD8 T reg Space of Disse MDSC Hepatocyte LSEC Kupffer cell Classical memory B cells replaced with atypicals Stellate cell Burton unpublished
7 Multiple immune defects in HBV infection Hepatocyte MAIT NK T reg Space of Disse LSEC MDSC Kupffer cell CD4 CD8 Stellate cell NK cells have defective IFN-g production Oliviero Gastro 2009 Bonorino J Hep 2009 Peppa PLoS Path 2010 Tjwa J Hep 2011
8 HBV hijacks the tolerogenic liver landscape Hepatocyte NK T reg Space of Disse LSEC Rapid, contact-dependent NK cell killing of HBV-specific T cells Kupffer cell CD4 CD8 Peppa JEM 2013 Boni Hepatol 2015 Huang JI 2017 Stellate cell Liver-resident NK cells have inducible TRAIL Stegmann et al, Sci Rep 2016 HBV-specific T cells upregulate TRAIL-R2 rendering them susceptible to NK cell-mediated deletion
9 HBV hijacks the tolerogenic liver landscape HBV-specific T cells are exhausted and pro-apoptotic Hepatocyte MAIT NK T reg Space of Disse LSEC MDSC Kupffer cell B cell CD4 CD8 Stellate cell Intrahepatic priming predisposes to Bim-mediated apoptosis Lopes et al JCI 2008 Ongoing exposure to co-inhibitory receptors and immunoregulatory cytokines drives exhaustion Dunn et al Gastroenterology 2009, Schurich et al Hepatology 2011, Das et al JI 2012 Nebbia et al PLoS One 2012, Schurich et al PLoS Path 2013
10 IL-12 synergises PD-1 rescue and overcomes mitochondrial defects
11 Going deeper than Checkpoint inhibitors: Targeting mitochondrial dysfunction Reversal of defects with mitochondrial antioxidants Mito-Q and MitoTempo
12 Metabolic checkpoints in HBV infection HBV-specific T cells are exhausted and pro-apoptotic Hepatocyte MAIT NK T reg Space of Disse LSEC MDSC Kupffer cell CD4 CD8 NK cells have defective IFN-g production NK cells delete HBV-specific T cells Stellate cell MDSC inhibit T cells through nutrient deprivation Das JEM 2008 Pallett Nat Med 2015
13 Expanded arginase+ myeloid-derived suppressor cells deprive T cells of arginine Hepatocyte Laura Pallett CD4 NK CD8 T reg Space of Disse LSEC MDSC Kupffer cell MDSC inhibit T cells through nutrient deprivation Stellate cell gmdsc
14 gmdsc (% of myeloid) Arginase I MFI ( 10 3 ) CD63 MFI Degranulating arginase+ gmdsc accumulate in the liver Hepatocyte Circulation NK T reg Space of Disse MDSC LSEC Kupffer cell CD4 CD8 Stellate cell Liver gmdsc: 60 Frequency Arginase Degranulation *** 30 ** 4,000 ** ,000 2, ,000 0 PBMC IHL 0 PBMC IHL 0 PBMC IHL
15 Metabolic regulation of T cells in viral hepatitis gmdsc arginase1 depletes extracellular arginine Pallett et al, Nat Med 2015 T cell arginase2 depletes intracellular arginine Geiger et al, Cell 2016 Arginine starvation of T cells: Impairs T cell proliferation, survival & antiviral function?drives mitochondrial defects
16 Boosting immunity in HBV: will it be safe? The trade-off between immunity and immunopathology HBV is a non-cytopathic virus Resultant liver disease is immune-mediated Immune responses e.g. CD8 T cells can mediate protection and liver injury Hepatic flares an inevitable result of effective immune boosting? Minimise antigen load need studies on extent of infected hepatocytes Select patients with good liver reserve Focus T cell boosting on HBV-specific component Develop adjunctive approaches to limit collateral damage
17 Which patients should be targeted for HBV functional cure? No consensus May vary depending on therapeutic strategy Suppressed on antivirals +/- prior HBeAg seronconversion Low level carriers Consider early in course of disease/younger patients -early HBV integration -major pool of infection -subtle liver damage -immune system less exhausted : Experimental immunotherapies can be tested first in HBV-related HCC e.g. Nivolumab
18 Tissue-resident T cells: front-line sentinels Laura Pallett Circulation Liver
19 CD103 % CD69 + CD103 + CD8+ T cells (as % of CD8+) CD8 T cells expressing tissue-retention signals sequestered in healthy human liver Blood Liver Healthy liver CRC margin Perfusate **** **** **** CD69 + CD103 + tissue-resident population CD69 0 Blood Liver 16 colour flow cytometry of 54 fresh liver samples Transcriptionally distinct: T-bet lo Eomes lo Blimp-1 hi Hobit lo Pallett et al J Exp Med 2017
20 (% CD45RA - ) (% CD45RA - ) (% CD45RA - ) Expansion of liver-resident CD8 T cell compartment in HBV immune controllers 60 **** 80 **** % CD69 + CD103 + T RM Blood Liver HBV % CD69 + CD103 + T RM Control HBV % CD69 + CD103 + T RM **** ** * 0 2x10 3 2x10 3-2x10 5 Viral load (IU/ml) 2x10 5 healthy
21 Multispecific HBV-specific T cells compartmentalised in the liver following HBV resolution Resolved HBV: sag-, anti-hbc+ Only reactivate upon immune suppression Gold-standard immune response to HBV Liver immunity never previously studied in this setting Overnight peptide stimulation of liver perfusate from HBV resolved donor:
22 Tissue-resident T cells in the human liver: Poised for frontline defence Hepatocyte NK T reg Space of Disse LSEC Kupffer cell CD4 CD8 Stellate cell Define signature of tissue-resident CD8 T cells in human liver --cannot be sampled in periphery -expand in HBV especially in those with good viral control -features that instruct their retention, survival, rapid non-cytolytic antiviral function -signals capable of recapitulating their induction Aim for induction of tissue-resident memory cells for functional cure Need for liver sampling in functional cure studies
23 Ross Lopes Abhishek Das Claire Dunn Pooja Khanna Lorenzo Micco Gaia Nebbia Wei-Chen Huang Simran Singh Itziar Otano Kasha Singh Dimitra Peppa Emily Colbeck UCL collaborators Niclas Thomas Nathan Davies Victoria Male Guiseppe Fusai Eleni Nastouli Richard Gilson Amir Gander Brian Davidson Francis Robertson William Rosenberg Tu Vinh Luong Acknowledgements Division of Infection and Immunity, UCL Barts & the London Hospital Upkar Gill Jyoti Hansi Patrick Kennedy All healthy donors, patients and clinic staff Laura Pallett Kerstin Stegmann Anna Schurich Jessica Davies Nicholas Easom Alice Burton Nathalie Schmidt Leo Swadling Mariana Diniz Kornelija Suveizdyte Oliver Amin University of Dundee Linda Sinclair Doreen Cantrell A*Star, Singapore Antonio Bertoletti
Checkpoint inhibitors for HBV cure
Checkpoint inhibitors for HBV cure Mala Maini Division of Infection and Immunity UCL, London Toronto HBV Cure 2016 Reversal of T cell exhaustion: the goal of checkpoint inhibitors CD8 T cells Granzyme
More informationCHRONIC HEPATITIS B VIRUS Prospects for Cure
VIRAL HEPATITIS and CO-INFECTION with HIV Bucharest, Romania, 6-7 October, 2016 CHRONIC HEPATITIS B VIRUS Prospects for Cure Patrick T. F. Kennedy Reader in Hepatology & Consultant Hepatologist Blizard
More informationRole of Innate Immunity in Hepatitis B Virus Infection Adam J. Gehring, Ph.D.
Role of Innate Immunity in Hepatitis B Virus Infection Adam J. Gehring, Ph.D. Biology Lead Toronto Centre for Liver Disease Toronto General Hospital Research Institute University Health Network (UHN) HBV
More informationWill Antigen Depletion Restore HBVspecific
Will Antigen Depletion Restore HBVspecific Immunity? Adam J. Gehring, Ph.D. Biology Lead Toronto Centre for Liver Disease University Health Network (UHN) Assistant Professor Department of Immunology University
More informationC. Ferrari Unit of Infectious Diseases and Hepatology Laboratory of Viral Immunopathology Azienda Ospedaliero-Universitaria di Parma Italy
HBV and the immune response C. Ferrari Unit of Infectious Diseases and Hepatology Laboratory of Viral Immunopathology Azienda Ospedaliero-Universitaria di Parma Italy List of topics - Kinetics of immune
More informationHBV and the immune response
HBV and the immune response C. Ferrari Unit of Infectious Diseases and Hepatology Laboratory of Viral Immunopathology Azienda Ospedaliero-Universitaria di Parma Italy List of topics - Kinetics of immune
More informationNew insights into CD8+ T cell function and regulation. Pam Ohashi Princess Margaret Cancer Centre
New insights into CD8+ T cell function and regulation Pam Ohashi Princess Margaret Cancer Centre New insights into CD8+ T cell function and regulation Pam Ohashi Princess Margaret Cancer Centre No Disclosures
More informationAre Immune Modulators Really Needed to Cure HBV infection?
Are Immune Modulators Really Needed to Cure HBV infection? Harry L.A. Janssen Francis Family Chair of Hepatology Director Toronto Centre for Liver Disease University Health Network University of Toronto,
More informationWhy do we need new HBV treatment and what is our definition for cure?
Why do we need new HBV treatment and what is our definition for cure? Harry L.A. Janssen Francis Family Chair of Hepatology Director Toronto Centre for Liver Disease University Health Network University
More informationHepatitis virus immunity. Mar 9, 2005 Rehermann and Nascimbeni review Crispe review
Hepatitis virus immunity Mar 9, 2005 Rehermann and Nascimbeni review Crispe review HBV & HCV infection outcomes Both viruses cause immune-mediated active and chronic hepatitis HBV Vertical transmission
More informationDarwinian selection and Newtonian physics wrapped up in systems biology
Darwinian selection and Newtonian physics wrapped up in systems biology Concept published in 1957* by Macfarland Burnet (1960 Nobel Laureate for the theory of induced immune tolerance, leading to solid
More informationImmune Checkpoints. PD Dr med. Alessandra Curioni-Fontecedro Department of Hematology and Oncology Cancer Center Zurich University Hospital Zurich
Immune Checkpoints PD Dr med. Alessandra Curioni-Fontecedro Department of Hematology and Oncology Cancer Center Zurich University Hospital Zurich Activation of T cells requires co-stimulation Science 3
More informationPersistent infection with hepatitis B virus (HBV)
Role of the Coinhibitory Receptor Cytotoxic T Lymphocyte Antigen-4 on Apoptosis-Prone CD8 T Cells in Persistent Hepatitis B Virus Infection Anna Schurich, 1 * Pooja Khanna, 1,2 * A. Ross Lopes, 1 Ki Jun
More informationHBV Novel Therapies Maria Buti MD, PhD
HBV Novel Therapies Maria Buti MD, PhD Liver Unit, Internal Medicine Department Vall d Hebron Hospital CONFLICT OF INTEREST I have financial relationships to disclose within the past 12 months relevant
More informationTim-3 as a target for tumor immunotherapy
Tim-3 as a target for tumor immunotherapy Ana Carrizosa Anderson Brigham and Women s Hospital Harvard Medical School Disclosures A portion of the work has been performed as part of a sponsored research
More informationSynergistic combinations of targeted immunotherapy to combat cancer
Synergistic combinations of targeted immunotherapy to combat cancer Myung Ah Lee, M.D., Ph. D Division of Medical Oncology, Hepato-biliary pancreatic cancer center Seoul St. Mary s hospital, The Catholic
More informationTumor Microenvironment and Immune Suppression
Tumor Microenvironment and Immune Suppression Hassane M. Zarour,, MD Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh Cancer Institute Hallmarks of Cancer: The Next Generation
More informationHepatitis B Cure: from discovery to regulatory endpoints in HBV clinical research A summary of the AASLD/EASL statement
Hepatitis B Cure: from discovery to regulatory endpoints in HBV clinical research A summary of the AASLD/EASL statement Fabien Zoulim Service d hépatologie, Hospices Civils de Lyon INSERM U1052, Cancer
More informationGeneral Overview of Immunology. Kimberly S. Schluns, Ph.D. Associate Professor Department of Immunology UT MD Anderson Cancer Center
General Overview of Immunology Kimberly S. Schluns, Ph.D. Associate Professor Department of Immunology UT MD Anderson Cancer Center Objectives Describe differences between innate and adaptive immune responses
More informationMicro 204. Cytotoxic T Lymphocytes (CTL) Lewis Lanier
Micro 204 Cytotoxic T Lymphocytes (CTL) Lewis Lanier Lewis.Lanier@ucsf.edu Lymphocyte-mediated Cytotoxicity CD8 + αβ-tcr + T cells CD4 + αβ-tcr + T cells γδ-tcr + T cells Natural Killer cells CD8 + αβ-tcr
More informationOncolytic Virotherapy: Targeting Cancer Stem Cells
Oncolytic Virotherapy: Targeting Cancer Stem Cells Cancer Stem Cells (CSCs) or Cancer Initiating Cells (CICs) A consensus of five defining criteria has been established to affirm the existence of CICs:
More informationInfection of parenchymal organs with noncytopathic. Increased Levels of Arginase in Patients With Acute Hepatitis B Suppress Antiviral T Cells
GASTROENTEROLOGY 2012;143:78 87 Increased Levels of Arginase in Patients With Acute Hepatitis B Suppress Antiviral T Cells ELENA SANDALOVA,* DILETTA LACCABUE, CAROLINA BONI, TSUNAMASA WATANABE, ANTHONY
More informationWhats new on HBsAg and other markers for HBV infection? Christoph Höner zu Siederdissen
Whats new on HBsAg and other markers for HBV infection? Christoph Höner zu Siederdissen Why diagnostic markers are important They are the basis for clinical decision makings treatment or no treatment?
More informationConsensus AASLD-EASL HBV Treatment Endpoint and HBV Cure Definition
Consensus AASLD-EASL HBV Treatment Endpoint and HBV Cure Definition Anna S. Lok, MD, DSc Alice Lohrman Andrews Professor in Hepatology Director of Clinical Hepatology Assistant Dean for Clinical Research
More informationHepatitis B New Therapies
Hepatitis B New Therapies Richard K. Sterling, MD, MSc, FACP, FACG, FAASLD, AGAF VCU Hepatology Professor of Medicine Chief, Section of Hepatology Fellowship Director, Transplant Hepatology Virginia Commonwealth
More informationTherapeutic immunization strategies in chronic hepatitis B
Therapeutic immunization strategies in chronic hepatitis B Mengji Lu Institut für Virologie Universitätsklinkum Essen Falk Symposium Berlin, 04. October 2005 The aim of therapeutic immunization to achieve
More informationHepatitis B and D Update on clinical aspects
Hepatitis B and D Update on clinical aspects B. Müllhaupt Gastroenterology and Hepatology Swiss Transplant and HPB-Center University Hospital Zurich beat.muellhaupt@usz.ch B.M. 11.11.17 Hepatitis Strategy
More informationSpecial situations: Patients with liver metastasis or liver primary tumor. Erika Martinelli, MD PhD Medical Oncologist
Special situations: Patients with liver metastasis or liver primary tumor Erika Martinelli, MD PhD Medical Oncologist Outline: Liver (anatomy, basic functions) Liver Immuno-landscape Immuno-landscape in
More informationCytotoxicity assays. Rory D. de Vries, PhD 1. Viroscience lab, Erasmus MC, Rotterdam, the Netherlands
Cytotoxicity assays Rory D. de Vries, PhD 1 1 Viroscience lab, Erasmus MC, Rotterdam, the Netherlands Anti-influenza immunity Humoral / CD4+ / CD8+ / NK? Function of CTL Elimination of virus-infected cells?
More informationShiv Pillai Ragon Institute, Massachusetts General Hospital Harvard Medical School
CTLs, Natural Killers and NKTs 1 Shiv Pillai Ragon Institute, Massachusetts General Hospital Harvard Medical School CTL inducing tumor apoptosis 3 Lecture outline CD8 + Cytotoxic T lymphocytes (CTL) Activation/differentiation
More informationApoptosis in chronic hepatitis C
Apoptosis in chronic hepatitis C Dr med. Anna Parfieniuk-Kowerda Department of Infectious Diseases and Hepatology Medical University of Bialystok Poland APOPTOSIS Apoptosis - type I programmed cell death
More informationInduction and Clearance of Latent HIV Infection:
214 Towards an HIV Cure symposium Melbourne Induction and Clearance of Latent HIV Infection: an Ex-Vivo Assessment of Immune Effectors using Cells from ART-treated Patients DM Margolis 1, C Garrido 1,
More informationHepatitis B. ECHO November 29, Joseph Ahn, MD, MS Associate Professor of Medicine Director of Hepatology Oregon Health & Science University
Hepatitis B ECHO November 29, 2017 Joseph Ahn, MD, MS Associate Professor of Medicine Director of Hepatology Oregon Health & Science University Disclosures Advisory board Gilead Comments The speaker Joseph
More informationNatural History of Chronic Hepatitis B
Natural History of Chronic Hepatitis B Anna SF Lok, MD Alice Lohrman Andrews Professor in Hepatology Director of Clinical Hepatology Assistant Dean for Clinical Research University of Michigan Ann Arbor,
More informationScott Abrams, Ph.D. Professor of Oncology, x4375 Kuby Immunology SEVENTH EDITION
Scott Abrams, Ph.D. Professor of Oncology, x4375 scott.abrams@roswellpark.org Kuby Immunology SEVENTH EDITION CHAPTER 13 Effector Responses: Cell- and Antibody-Mediated Immunity Copyright 2013 by W. H.
More informationImmunotherapy for Chronic Hepatitis B Virus Infection
Gut and Liver, Vol. 12, No. 5, September 2018, pp. 497-507 Review Immunotherapy for Chronic Hepatitis B Virus Infection Antonio Bertoletti 1,2 and Nina Le Bert 1,2 1 Emerging Infectious Diseases Program,
More informationBlockade of Immunosuppressive Cytokines Restores NK Cell Antiviral Function in Chronic Hepatitis B Virus Infection
Blockade of Immunosuppressive Cytokines Restores NK Cell Antiviral Function in Chronic Hepatitis B Virus Infection Peppa, D; Micco, L; Javaid, A; Kennedy, PTF; Schurich, A; Dunn, C; Pallant, C; Ellis,
More information4th International HIV/Viral Hepatitis Co-Infection Meeting
4th International HIV/Viral Hepatitis Co-Infection Meeting The Rocky Road to Viral Hepatitis Elimination: Assuring access to antiviral therapy for ALL co-infected patients from low to high income settings
More informationAre booster immunisations needed for lifelong hepatitis B immunity?
Are booster immunisations needed for lifelong hepatitis B immunity? European Consensus Group on Hepatitis B immunity, following meeting in Florence in October 1998 To date there are no data to support
More informationAllergy and Immunology Review Corner: Chapter 19 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD.
Allergy and Immunology Review Corner: Chapter 19 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD. Chapter 19: Tolerance, Autoimmunity, and Autoinflammation Prepared
More informationNatural Killer Cells Are Characterized by the Concomitantly Increased Interferon-c and Cytotoxicity in Acute Resolved Hepatitis B Patients
Natural Killer Cells Are Characterized by the Concomitantly Increased Interferon-c and Cytotoxicity in Acute Resolved Hepatitis B Patients Juanjuan Zhao 1., Yonggang Li 2., Lei Jin 3, Shuye Zhang 3, Rong
More informationAlcoholic hepatitis is a drug-induced disorder
Alcoholic hepatitis is a drug-induced disorder Gyongyi Szabo, MD, PhD Professor of Medicine University of Massachusetts Medical School Source: 2 Sobernation.com Clinical Progression of ALD Mortality Acute
More information2/16/2018. The Immune System and Cancer. Fatal Melanoma Transferred in a Donated Kidney 16 years after Melanoma Surgery
C007: Immunology of Melanoma: Mechanisms of Immune Therapies Delphine J. Lee, MD, PhD Chief and Program Director, Dermatology, Harbor UCLA Medical Center Principal Investigator, Los Angeles Biomedical
More informationShort Duration DAA Therapy for Hepatitis C: How Short Can We Go?
Short Duration DAA Therapy for Hepatitis C: How Short Can We Go? Shyam Kottilil MD, Ph.D. Institute of Human Virology, University of Maryland, Baltimore, MD HEPDART Kona, HI Disclosures Received research
More informationAnti-HBc: state of the art what is the CORE of the issues?
Anti-HBc: state of the art what is the CORE of the issues? Robert G Gish MD Adjunct Professor Stanford University Medical Director Hepatitis B Foundation Disclosures: See robertgish.com If you wish an
More informationEffector mechanisms of cell-mediated immunity: Properties of effector, memory and regulatory T cells
ICI Basic Immunology course Effector mechanisms of cell-mediated immunity: Properties of effector, memory and regulatory T cells Abul K. Abbas, MD UCSF Stages in the development of T cell responses: induction
More informationHCV eradication with direct acting antivirals (DAAs)? Why is viral cure possible in HCV? Emilie Estrabaud
HCV eradication with direct acting antivirals (DAAs)? Why is viral cure possible in HCV? Emilie Estrabaud Service d Hépatologie et INSERM UMR1149, AP-HP Hôpital Beaujon, Paris, France. emilie.estrabaud@inserm.fr
More informationDaratumumab: Uncovering a novel mechanism of action for an approved antibody therapy
Daratumumab: Uncovering a novel mechanism of action for an approved antibody therapy Dr. Kate Sasser, PhD Corporate VP, Translational Research December 14 th, 2017 CD38 is ubiquitously expressed in Myeloma
More informationAcute Hepatitis B Virus Infection with Recovery
Hepatitis B: Clear as Mud Melissa Osborn, MD, MSCR Assistant Professor Emory University School of Medicine Atlanta, GA 1 Objectives 1. Distinguish the various stages in the natural history of chronic hepatitis
More informationDon t interfere My first choice is always nucs!
Don t interfere My first choice is always nucs! Robert G Gish MD Professor Consultant Stanford University Medical Director, Hepatitis B Foundation Singapore Viral Hepatitis Meeting 2014 1 Disclosures Dr
More informationSERUM HBV-RNA LEVELS DECLINE SIGNIFICANTLY IN CHRONIC HEPATITIS B PATIENTS DOSED WITH THE NUCLEIC-ACID POLYMER REP 2139-Ca
SERUM HBV-RNA LEVELS DECLINE SIGNIFICANTLY IN CHRONIC HEPATITIS B PATIENTS DOSED WITH THE NUCLEIC-ACID POLYMER REP 2139-Ca Louis Jansen 1,2, Andrew Vaillant 3, Karel van Dort 1, Femke Stelma 1,2, Neeltje
More informationLa riattivazione dell epatite virale nel paziente in terapia biologica
La riattivazione dell epatite virale nel paziente in terapia biologica Claudio Puoti S.C. di Medicina Interna e Medicina Epato-Gastroenterologica Osp. di Marino-Frascati - Roma Patterns of HBV-related
More informationTherapeutic Efficacy of a TLR7 Agonist for HBV Chronic Infection in Chimpanzees
Therapeutic Efficacy of a TLR7 Agonist for HBV Chronic Infection in Chimpanzees Robert Lanford 1, Bernadette Guerra 1, Deborah Chavez 1, Vida L. Hodara 1, Xubin Zheng 2, Grushenka Wolfgang 3, Daniel B.
More informationCD4 + CD25 high Foxp3 + T regulatory cells kill autologous CD8(+) and CD4(+) T cells using Fas/FasL- and Granzyme B- mediated pathways
CD4 + CD25 high Foxp3 + T regulatory cells kill autologous CD8(+) and CD4(+) T cells using Fas/FasL- and Granzyme B- mediated pathways Laura Strauss, Christoph Bergmann, Theresa L. Whiteside University
More informationHepatitis delta: often forgotten?
15 th Annual Resistance and Antiviral Therapy Meeting Dr Sarah Hughes King s College Hospital, London Thursday 29 September 2011, Royal College of Physicians, London Hepatitis delta: often forgotten? Dr
More informationHD1 (FLU) HD2 (EBV) HD2 (FLU)
ramer staining + anti-pe beads ramer staining a HD1 (FLU) HD2 (EBV) HD2 (FLU).73.11.56.46.24 1.12 b CD127 + c CD127 + d CD127 - e CD127 - PD1 - PD1 + PD1 + PD1-1 1 1 1 %CD127 + PD1-8 6 4 2 + anti-pe %CD127
More informationHBV Cure Definition and New Drugs in Development
HBV Cure Definition and New Drugs in Development Harry L.A. Janssen Francis Family Chair of Hepatology Director Toronto Centre for Liver Disease University Health Network University of Toronto, Canada
More informationPriming the Immune System to Kill Cancer and Reverse Tolerance. Dr. Diwakar Davar Assistant Professor, Melanoma and Phase I Therapeutics
Priming the Immune System to Kill Cancer and Reverse Tolerance Dr. Diwakar Davar Assistant Professor, Melanoma and Phase I Therapeutics Learning Objectives Describe the role of the immune system in cancer
More informationNKTR-214 plus NKTR-262, a Scientifically-Guided Rational Combination Approach for Immune Oncology
plus NKTR-262, a Scientifically-Guided Rational Combination Approach for Immune Oncology Jonathan Zalevsky SVP, Biology and Preclinical Development Nektar Therapeutics World Preclinical Congress, 2017
More informationBASIC MECHANISM OF TUMOR IMMUNE SUPPRESSION
BASIC MECHANISM OF TUMOR IMMUNE SUPPRESSION Zihai Li, M.D., Ph.D. Leader, Cancer Immunology Program Hollings Cancer Center Medical University of South Carolina (MUSC) DISCLOSURE GOALS Understand that immune
More informationHepatitis B: An Update COPYRIGHT
Hepatitis B: An Update Sanjiv Chopra, M.D. Professor of Medicine Harvard Medical School James Tullis Firm Chief Department of Medicine Beth Israel Deaconess Medical Center A Tale of Serendipity Baruch
More informationSupplementary Table 1 Clinicopathological characteristics of 35 patients with CRCs
Supplementary Table Clinicopathological characteristics of 35 patients with CRCs Characteristics Type-A CRC Type-B CRC P value Sex Male / Female 9 / / 8.5 Age (years) Median (range) 6. (9 86) 6.5 (9 76).95
More informationChronic viral hepatitis and liver disease in Belgium Pierre Deltenre
Chronic viral hepatitis and liver disease in Belgium Pierre Deltenre Brussels, November 7, 2017 Hepatitis B and C in Belgium What we need to know 1. Who is at risk of infection? 2. What is the natural
More informationCELLULAR AND MOLECULAR REQUIREMENTS FOR REJECTION OF B16 MELANOMA IN THE SETTING OF REGULATORY T CELL DEPLETION AND HOMEOSTATIC PROLIFERATION
CELLULAR AND MOLECULAR REQUIREMENTS FOR REJECTION OF B16 MELANOMA IN THE SETTING OF REGULATORY T CELL DEPLETION AND HOMEOSTATIC PROLIFERATION Justin Kline 1, Long Zhang 1, and Thomas F. Gajewski 1,2 Departments
More information5% of patients with genetic immunodeficiency develop a cancer during their lifetime (200x)
Immune surveillance 5% of patients with genetic immunodeficiency develop a cancer during their lifetime (200x) Transplanted patients following an immunosuppressor therapy are 80 times more likely to develop
More informationHepatitis B Virus infection: virology
Hepatitis B Virus infection: virology 167 Falk Symposium: Liver under constant attack from fat to viruses III Falk Gastro-Konferenz 17.-21. September 2008 Congress Centrum Mainz Maura Dandri Department
More informationEx-Vivo heat shock protein 70-peptide-activated, autologous natural killer cells adoptive therapy: from the bench to the clinic
Ex-Vivo heat shock protein 70-peptide-activated, autologous natural killer cells adoptive therapy: from the bench to the clinic isbtc 10-13 November 2005 Valeria Milani, MD, PhD Munich Agenda 1. NK ligands
More informationAn HCV Vaccine: Can we get there?
An HCV Vaccine: Can we get there? Andrea L. Cox, MD,PhD Viral Hepatitis Center No Conflicts of Interest Outline Reasons to develop an HCV vaccine What constitutes protective immunity to HCV What challenges
More informationImmunology CANCER IMMUNOLOGY
Immunology د. عائدة الدرزي Lec. 6 CANCER IMMUNOLOGY Oncogenesis (passes through two stages): 1- Reversible change Normal transformed cells 2- Irreversible change Transformed oncogenic cells Factors causing
More informationModeling Kinetics of HBV Infection and Recommendations for Moving Forward
Modeling Kinetics of HBV Infection and Recommendations for Moving Forward Alan S. Perelson Theoretical Biology and Biophysics Los Alamos National Laboratory Los Alamos, NM HBV Models Hepatology 1999 Tsiang
More informationHEPATITIS B: WHO AND WHEN TO TREAT?
HEPATITIS B: WHO AND WHEN TO TREAT? George V. Papatheodoridis Professor in Medicine & Gastroenterology Medical School of National & Kapodistrian University of Athens Director of Academic Department of
More informationEffects of Inarigivir (SB9200) Therapy on Immune Responses in Patients with Chronic Hepatitis B (CHB)
Effects of (SB9200) Therapy on Immune Responses Patients with Chronic Hepatitis B (CHB) Renae Walsh 1, Rachel Hammond 1, Kathy Jackson 1, Ros Edwards 1, Chelsea Macfarlane 2, Radhakrishnan P. Iyer 2, Man
More informationClinical Management of Hepatitis B WAN-CHENG CHOW DEPARTMENT OF GASTROENTEROLOGY & HEPATOLOGY SINGAPORE GENERAL HOSPITAL
Clinical Management of Hepatitis B WAN-CHENG CHOW DEPARTMENT OF GASTROENTEROLOGY & HEPATOLOGY SINGAPORE GENERAL HOSPITAL The World Health Organisation recent initiatives on HBV infection Launching of the
More informationBasic Principles of Tumor Immunotherapy and Mechanisms of Tumor Immune Suppression. Bryon Johnson, PhD
Basic Principles of Tumor Immunotherapy and Mechanisms of Tumor Immune Suppression Bryon Johnson, PhD Disclosures There will be discussion about the use of products for non-fda indications in this presentation.
More informationRegulation of anti-tumor immunity through migration of immune cell subsets within the tumor microenvironment Thomas F. Gajewski, M.D., Ph.D.
Regulation of anti-tumor immunity through migration of immune cell subsets within the tumor microenvironment Thomas F. Gajewski, M.D., Ph.D. Professor, Departments of Pathology and Medicine Program Leader,
More informationImmunobiology of hepatitis B virus infection
bs_bs_banner doi: 10.1111/hepr.12439 Review Article Immunobiology of hepatitis B virus infection Masanori Isogawa and Yasuhito Tanaka Department of Virology and Liver Unit, Nagoya City University Graduate
More informationWhere a licence is displayed above, please note the terms and conditions of the licence govern your use of this document.
Reply to: To target or not to target viral antigens in HBV related HCC? by Buschow et al Qasim, Waseem; Brunetto, Maurizia; Gehring, Adam; Maini, Mala; Bonino, Ferruccio; Stauss, Hans; Bertoletti, Antonio
More informationBasics of hepatitis B diagnostics. Dr Emma Page MRCP MD(Res) Locum Consultant Sexual Health & Virology
Basics of hepatitis B diagnostics Dr Emma Page MRCP MD(Res) Locum Consultant Sexual Health & Virology Basics of hepatitis B diagnostics Background Epidemiology Morphology Life-cycle Diagnostic markers
More informationSerum Hepatitis B Surface Antigen Levels Help Predict Disease Progression in Patients With Low Hepatitis B Virus Loads. Hepatology Feb 2013
Serum Hepatitis B Surface Antigen Levels Help Predict Disease Progression in Patients With Low Hepatitis B Virus Loads Hepatology Feb 2013 Hepatitis B Surface Antigen HBsAg is the glycosylated envelope
More informationHepatitis B Diagnosis and Management. Marion Peters University of California San Francisco
Hepatitis B Diagnosis and Management Marion Peters University of California San Francisco COI Spouse works for Hoffmann-La Roche HBV is a life long, dynamic disease Changes over time Risk of end stage
More informationBiology of Immune Aging
Biology of Immune Aging Jorg J. Goronzy Stanford University Immune deficiency Increase morbidity and mortality from infections Poor vaccine responses Cancer Immune Aging Chronic inflammation Coronary artery
More informationImmune response. This overview figure summarizes simply how our body responds to foreign molecules that enter to it.
Immune response This overview figure summarizes simply how our body responds to foreign molecules that enter to it. It s highly recommended to watch Dr Najeeb s lecture that s titled T Helper cells and
More informationBasic Principles of Tumor Immunotherapy. Ryan J. Sullivan, M.D. Massachusetts General Hospital Cancer Center Boston, MA
Basic Principles of Tumor Immunotherapy Ryan J. Sullivan, M.D. Massachusetts General Hospital Cancer Center Boston, MA Disclosures Consulting Fees: Biodesix, Novartis Pharmaceuticals Other: Boehringer
More informationSupplementary materials: Predictors of response to pegylated interferon in chronic hepatitis B: a
Supplementary materials: Predictors of response to pegylated interferon in chronic hepatitis B: a real-world hospital-based analysis Yin-Chen Wang 1, Sien-Sing Yang 2*, Chien-Wei Su 1, Yuan-Jen Wang 3,
More informationDisclosures. Pathogenesis of Autoimmunity Normal immune response: 11/5/2011. Methotrexate and JUN Pathway Activation in Rheumatoid Arthritis
Methotrexate and JUN Pathway Activation in Rheumatoid Arthritis Disclosures N. Olsen and T. Aune are co-founders of ArthroChip LLC. Nancy J. Olsen Penn State MS Hershey Medical Center Thomas M. Aune Vanderbilt
More informationDiseases of Immunity 2017 CL Davis General Pathology. Paul W. Snyder, DVM, PhD Experimental Pathology Laboratories, Inc.
Diseases of Immunity 2017 CL Davis General Pathology Paul W. Snyder, DVM, PhD Experimental Pathology Laboratories, Inc. Autoimmunity Reflects a loss of immunologic tolerance Mechanisms Auto-antibodies
More informationHuman Immunodeficiency Virus Type-1 Myeloid Derived Suppressor Cells Inhibit Cytomegalovirus Inflammation through Interleukin-27 and B7-H4
Human Immunodeficiency Virus Type-1 Myeloid Derived Suppressor Cells Inhibit Cytomegalovirus Inflammation through Interleukin-27 and B7-H4 Ankita Garg, Rodney Trout and Stephen A. Spector,,* Department
More informationHLA-E restricted responses in Tuberculosis
HLA-E restricted responses in Tuberculosis Simone A. Joosten Dept. of Infectious Diseases LEIDEN UNIVERSITY MEDICAL CENTER Unconventional immunity Conventional immunity: T cells reactive to complexes of
More informationViral Hepatitis The Preventive Potential of Antiviral Therapy. Thomas Berg
Viral Hepatitis The Preventive Potential of Antiviral Therapy Thomas Berg Therapeutic and preventive strategies in patients with hepatitis virus infection Treatment of acute infection Treatment of chronic
More informationDistinct Metabolic Requirements of Exhausted and Functional Virus- Specific CD8 T Cells in the Same Host.
Distinct Metabolic Requirements of Exhausted and Functional Virus- Specific CD8 T Cells in the Same Host. Schurich, A; Pallett, LJ; Jajbhay, D; Wijngaarden, J; Otano, I; Gill, US; Hansi, N; Kennedy, PT;
More informationHepatitis C Virus and Cytokine Responses
Hepatitis C Virus and Cytokine Responses Eui-Cheol Shin, M.D., Ph.D. Laboratory of Immunology & Infectious Diseases (LIID), Graduate School of Medical Science & Engineering (GSMSE), KAIST Daejeon, Korea
More informationHBV Cure Overview of Viral and Immune Targets
HBV Cure Overview of Viral and Immune Targets Harry L.A. Janssen Francis Family Chair of Hepatology Director Toronto Centre for Liver Disease University Health Network University of Toronto, Canada October
More informationCornerstones of Hepatitis B: Past, Present and Future
Cornerstones of Hepatitis B: Past, Present and Future Professor Man-Fung Yuen Queen Mary Hospital The University of Hong Kong Hong Kong 1 Outline Past Natural history studies Development of HBV-related
More information6/9/2015. Eugene R. Schiff, MD, MACP, FRCP, MACG, AGAF, FAASLD Director, Schiff Center for Liver Diseases University of Miami
Grant/Research Support: AbbVie, BMS, Gilead, Merck, Orasure Technologies, Roche Molecular, Janssen, Discovery Life Sciences, Beckman Coulter, Inc., Siemens Corporation, MedMira Inc., Conatus Eugene R.
More informationCell Mediated Immunity CELL MEDIATED IMMUNITY. Basic Elements of Cell Mediated Immunity (CMI) Antibody-dependent cell-mediated cytotoxicity (ADCC)
Chapter 16 CELL MEDIATED IMMUNITY Cell Mediated Immunity Also known as Cellular Immunity or CMI The effector phase T cells Specificity for immune recognition reactions TH provide cytokines CTLs do the
More informationSupplementary Figures
Supplementary Figures Supplementary Figure 1. NKT ligand-loaded tumour antigen-presenting B cell- and monocyte-based vaccine induces NKT, NK and CD8 T cell responses. (A) The cytokine profiles of liver
More informationBible Class: Hepatitis B Virus Infection
Bible Class: Hepatitis B Virus Infection Nasser Semmo UVCM, Hepatology What is the HBV prevalence? 2 Hepatitis B Worldwide approx. 350 Mio. chronically infected with HBV Approx. 40% of the world population:
More information26/09/2014. Chronic HBV Infection (n = >370 million world-wide n = 218,000 in Australia) HBV REACTIVATION
Chronic HBV (n = >37 million world-wide n = 218, in Australia) HBV REACTIVATION PLAYING WITH FIRE Maggie Bassendine 5-3 Yrs HBV (up to 2 billion people world-wide, up to 2 million in Australia) 5-3 Yrs
More informationCommercially available HLA Class II tetramers (Beckman Coulter) conjugated to
Class II tetramer staining Commercially available HLA Class II tetramers (Beckman Coulter) conjugated to PE were combined with dominant HIV epitopes (DRB1*0101-DRFYKTLRAEQASQEV, DRB1*0301- PEKEVLVWKFDSRLAFHH,
More informationChoice of Oral Drug for Hepatitis B: Status Asokananda Konar
Choice of Oral Drug for Hepatitis B: Status 2011 Asokananda Konar Chronic hepatitis B (CHB) is a global public health challenge with an estimated 350 to 400 million people with chronic HBV infection, despite
More information