Glioma cancer stem cells mediate immune suppression that can be reversed with STAT3 blockade
|
|
|
- Lester Hopkins
- 6 years ago
- Views:
Transcription
1 Glioma cancer stem cells mediate immune suppression that can be reversed with STAT3 blockade Jun Wei Department of Neurosurgery October 23, 2009
2 Immune suppression in Malignant Glioma Patients Mechanisms Immune suppressive cytokines (TGF-β, IL-, PGE2) Loss of antigen/mhc expression Lack of co-stimulation in the tumor microenvironment (induction of anergy) Induction of T cell apoptosis Expression of inhibitory costimulation (B7-H1) Enhanced Tregs Immune suppressive microglia/macrophages Cancer stem cells/cancer initiating cells? Manifestations Decreased delayed type hypersensitivity responses to recall antigens Diminished antibody responses Impaired T cell proliferation and responses to IL-2 Impaired cytotoxic/effector T cell responses T cell anergy/unresponsiveness Is there a common pathway?
3 The STAT3 pathway is active in many cancers including gliomas p-stat3 Expression in GBM Abou-Ghazal MK et al. Clinical Cancer Res. 2008, 14(24):
4 The STAT3 pathway is a key regulatory pathway in immune suppression Yu et al. Nature Reviews Immunology 7, (January 2007)
5 Glioma cancer stem cells (gcscs) gcscs possesses marked capacity for proliferation, self-renewal and differentiation. (Singh S, et al. Cancer Res. 2003, 63: ) gcscs can establish tumors with all of the classical features of human GBM. (Galli R, et al. Cancer Res. 2004, 64: ) gcscs mediate resistance of radiotherapy and chemotherapy. (Bao S, et al. Nature 2006: ; Murat A, et al. J Clin Oncol 2008: )
6 Hypothesis : gcscs contribute to the immune suppression evident in glioma patients and STAT-3 pathway blockade can reverse this immunosuppression
7 Properties of GBM Cancer Stem Cells (gcsc)/cancer initiating cells Form neurospheres Form infiltrating tumors Are induced to differentiate into various glia populations Express CD133 DMEM-F-12 supplemented with EGF (20ng/mL), bfgf and B27 (1:50) Tuj1/GFAP/DAPI ISOTYPE CD
8 The immune phenotype of gcscs are immune inhibitory MHC I MHC II CD % 1.6% 0.8% CD CD B7-H1 0.6% 6.3% 34.9%
9 gcscs inhibit T cell proliferation Medium (control) Anti-CD3/CD PHA 49.9 gcsc 1 gcsc 2 gcsc CFSE CD
10 gcscs induce FoxP3+ Tregs Medium (control) gcsc 1 (low CD133) gcsc 2 (medium CD133) gcsc 3 (high CD133) FoxP CD4 Medium (control) gcsc 1 gcsc 2 gcsc CFSE
11 gcscs induce T cell apoptosis Medium (control) gcsc 1 gcsc 2 gcsc AAD Annexin V
12 The degree of gcsc-mediated immune suppression correlates with in vivo tumorigenicity
13 Cytokines elaboration by gcsc screened by RayBio Cytokine Antibody Array and verified by ELISA TGF-β 76 (39-118) pg/ml IL- 0 pg/ml PGE (79-277) pg/ml Soluble Fas 0 pg/ml IL-6 0 pg/ml CCL-2 2 (0-391) pg/ml NO 0 pg/ml Galectin-3 2,600 (500-4,500) pg/ml
14 B7-H1 contributes to cell-contact dependent immune suppression
15 Inhibition of p-stat3 reverses immune suppression
16 WP66 restores immunological responses
17 Conclusions gcsc contribute to malignant glioma patient immune suppression by: Inhibition of T cell proliferation, activation and effector function Induction of T cell apoptosis (via Galectin-3, B7-H1) Stimulation of Tregs (via TGF-β, B7-H1) CD133 expression does not correlate with the degree of immune suppression The degree of gcsc mediated immune suppression inversely correlates with in vivo survival The immune suppressive properties of gcscs on T cell effector function and proliferation can be reversed with inhibitors of the p-stat3 pathway
18 Acknowledgements Amy Heimberger M.D. Jason Barr Ling-Yuan Kong Ph.D. Tony Wang M.D. Adam Wu M.D. David S. Yang Wei Sun Ph.D. Amit Sharma Lamonne Crutcher Collaborators Frederick Lang M.D. Waldemar Priebe Ph.D. Raymond Sawaya M.D. Howard Colman M.D. Ph.D. Joy Gumin Verlene Henry Funding support: National Institute of Health RO1-CA National Brain Tumor Society MDACC Institutional Research Grant Dr Marnie Rose Foundation Anthony Bullock Foundation
19 Conclusions 1. GBM cancer stem-like cells (gcscs) possess intrinsic immunosuppressive properties; 2. Immunosuppressive properties of the gcscs are reduced upon differentiation; 3. p-stat-3 inhibitor, WP66, can partially reverse immunosuppressive properties of the gcscs.
20 Future Direction 1. Identify the secreted product(s) from cancer stem cells mediating their immune suppressive properties; 2. Clarify mechanisms by which gcscs induce regulatory T cells; 3. Ascertain whether immunosuppressive properties of gcscs mainly depend on STAT-3 pathway.
21 Galectin-3 can induce T cell apoptosis 7-AAD Annexin V
22 The degree of gcsc mediated immune suppression does not correlate with CD133 expression
Tumor 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
CD4 + 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
Adaptive (acquired) immunity. Professor Peter Delves University College London
Adaptive (acquired) immunity Professor Peter Delves University College London p.delves@ucl.ac.uk Haematopoiesis Haematopoiesis Lymphocytes = adaptive response Recognition of pathogens by adaptive cells,
Tolerance, autoimmunity and the pathogenesis of immunemediated inflammatory diseases. Abul K. Abbas UCSF
Tolerance, autoimmunity and the pathogenesis of immunemediated inflammatory diseases Abul K. Abbas UCSF Balancing lymphocyte activation and control Activation Effector T cells Tolerance Regulatory T cells
Tolerance 2. Regulatory T cells; why tolerance fails. Abul K. Abbas UCSF. FOCiS
1 Tolerance 2. Regulatory T cells; why tolerance fails Abul K. Abbas UCSF FOCiS 2 Lecture outline Regulatory T cells: functions and clinical relevance Pathogenesis of autoimmunity: why selftolerance fails
Central tolerance. Mechanisms of Immune Tolerance. Regulation of the T cell response
Immunoregulation: A balance between activation and suppression that achieves an efficient immune response without damaging the host. Mechanisms of Immune Tolerance ACTIVATION (immunity) SUPPRESSION (tolerance)
Mechanisms of Immune Tolerance
Immunoregulation: A balance between activation and suppression that achieves an efficient immune response without damaging the host. ACTIVATION (immunity) SUPPRESSION (tolerance) Autoimmunity Immunodeficiency
Allergy 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
Effector 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
Immune Tolerance. Kyeong Cheon Jung. Department of Pathology Seoul National University College of Medicine
Immune Tolerance Kyeong Cheon Jung Department of Pathology Seoul National University College of Medicine Immune tolerance Unresponsiveness to an antigen that is induced by previous exposure to that antigen
SEVENTH EDITION CHAPTER
Judy Owen Jenni Punt Sharon Stranford Kuby Immunology SEVENTH EDITION CHAPTER 16 Tolerance, Autoimmunity, and Transplantation Copyright 2013 by W. H. Freeman and Company Immune tolerance: history * Some
Supplemental Figure 1. Signature gene expression in in vitro differentiated Th0, Th1, Th2, Th17 and Treg cells. (A) Naïve CD4 + T cells were cultured
Supplemental Figure 1. Signature gene expression in in vitro differentiated Th0, Th1, Th2, Th17 and Treg cells. (A) Naïve CD4 + T cells were cultured under Th0, Th1, Th2, Th17, and Treg conditions. mrna
CD90 + Human Dermal Stromal Cells Are Potent Inducers of FoxP3 + Regulatory T Cells
CD90 + Human Dermal Stromal Cells Are Potent Inducers of FoxP3 + Regulatory T Cells Karin Pfisterer, Karoline M Lipnik, Erhard Hofer and Adelheid Elbe-Bürger Journal of Investigative Dermatology (2015)
Immune 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
Analysis of regulatory T cell subsets in the peripheral blood of immunoglobulin A nephropathy (IgAN) patients
Analysis of regulatory T cell subsets in the peripheral blood of immunoglobulin A nephropathy (IgAN) patients S. Yang, B. Chen, J. Shi, F. Chen, J. Zhang and Z. Sun Department of Nephrology, Huaihe Hospital
VISTA, a novel immune checkpoint protein ligand that suppresses anti-tumor tumor T cell responses. Li Wang. Dartmouth Medical School
VISTA, a novel immune checkpoint protein ligand that suppresses anti-tumor tumor T cell responses Li Wang Dartmouth Medical School The B7 Immunoglobulin Super-Family immune regulators APC T cell Co-stimulatory:
Cellular Immune response. Jianzhong Chen, Ph.D Institute of immunology, ZJU
Cellular Immune response Jianzhong Chen, Ph.D Institute of immunology, ZJU Concept of adaptive immune response T cell-mediated adaptive immune response I. Concept of immune response A collective and coordinated
Lecture outline. Immunological tolerance and immune regulation. Central and peripheral tolerance. Inhibitory receptors of T cells. Regulatory T cells
1 Immunological tolerance and immune regulation Abul K. Abbas UCSF 2 Lecture outline Central and peripheral tolerance Inhibitory receptors of T cells Regulatory T cells 1 The immunological equilibrium:
Immunological Tolerance
Immunological Tolerance Introduction Definition: Unresponsiveness to an antigen that is induced by exposure to that antigen Tolerogen = tolerogenic antigen = antigen that induces tolerance Important for
Basic Immunology. Immunological tolerance. Cellular and molecular mechanisms of the immunological tolerance. Lecture 23 rd
Basic Immunology Lecture 23 rd Immunological tolerance Cellular and molecular mechanisms of the immunological tolerance Tolerated skin grafts on MHC (H2) identical mice TOLERANCE & AUTOIMMUNITY Upon encountering
Immune Regulation and Tolerance
Immune Regulation and Tolerance Immunoregulation: A balance between activation and suppression of effector cells to achieve an efficient immune response without damaging the host. Activation (immunity)
Supplementary Figure 1. IL-12 serum levels and frequency of subsets in FL patients. (A) IL-12
1 Supplementary Data Figure legends Supplementary Figure 1. IL-12 serum levels and frequency of subsets in FL patients. (A) IL-12 serum levels measured by multiplex ELISA (Luminex) in FL patients before
Objectives. Abbas Chapter 11: Immunological Tolerance. Question 1. Question 2. Question 3. Definitions
Objectives Abbas Chapter 11: Immunological Tolerance Christina Ciaccio, MD Children s Mercy Hospitals and Clinics February 1, 2010 To introduce the concept of immunologic tolerance To understand what factors
Cover Page. The handle holds various files of this Leiden University dissertation.
Cover Page The handle http://hdl.handle.net/1887/23854 holds various files of this Leiden University dissertation. Author: Marel, Sander van der Title: Gene and cell therapy based treatment strategies
Supplementary information. Characterization of c-maf + Foxp3 - Regulatory T Cells Induced by. Repeated Stimulation of Antigen-Presenting B Cells
Chien 1 Supplementary information Manuscript: SREP-16-42480A Characterization of c-maf + Foxp3 - Regulatory T Cells Induced by Repeated Stimulation of Antigen-Presenting B Cells Chien-Hui Chien 1, Hui-Chieh
Determinants of Immunogenicity and Tolerance. Abul K. Abbas, MD Department of Pathology University of California San Francisco
Determinants of Immunogenicity and Tolerance Abul K. Abbas, MD Department of Pathology University of California San Francisco EIP Symposium Feb 2016 Why do some people respond to therapeutic proteins?
Glioblastoma and CNS tumors
Glioblastoma and CNS tumors PRECEPTORSHIP PROGRAMME IMMUNO-ONCOLOGY Amsterdam, 1 October 2016 Patrick Roth Department of Neurology and Brain Tumor Center University Hospital Zurich Immunology in the CNS
Darwinian 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
Tolerance 2. Regulatory T cells; why tolerance fails. FOCiS. Lecture outline. Regulatory T cells. Regulatory T cells: functions and clinical relevance
1 Tolerance 2. Regulatory T cells; why tolerance fails Abul K. Abbas UCSF FOCiS 2 Lecture outline Regulatory T cells: functions and clinical relevance Pathogenesis of autoimmunity: why selftolerance fails
Regulation 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,
Cell isolation. Spleen and lymph nodes (axillary, inguinal) were removed from mice
Supplementary Methods: Cell isolation. Spleen and lymph nodes (axillary, inguinal) were removed from mice and gently meshed in DMEM containing 10% FBS to prepare for single cell suspensions. CD4 + CD25
T cell maturation. T-cell Maturation. What allows T cell maturation?
T-cell Maturation What allows T cell maturation? Direct contact with thymic epithelial cells Influence of thymic hormones Growth factors (cytokines, CSF) T cell maturation T cell progenitor DN DP SP 2ry
T Cell Receptor & T Cell Development
T Cell Receptor & T Cell Development Questions for the next 2 lectures: How do you generate a diverse T cell population with functional TCR rearrangements? How do you generate a T cell population that
T Lymphocyte Activation and Costimulation. FOCiS. Lecture outline
1 T Lymphocyte Activation and Costimulation Abul K. Abbas, MD UCSF FOCiS 2 Lecture outline T cell activation Costimulation, the B7:CD28 family Inhibitory receptors of T cells Targeting costimulators for
Immunological alterations in mice irradiated with low doses
Immunological alterations in mice irradiated with low doses "Frédéric Joliot-Curie" National Research Institute for Radiobiology and Radiohygiene, Budapest, Hungary The structure of the immune system INNATE
ankylosing spondylitis Department of Clinical Immunology, Xijing Hospital, The Fourth Military
Functional defects in CD4 + CD25 high FoxP3 + regulatory cells in ankylosing spondylitis Huifang Guo 1, 2, 3, Ming Zheng 1, 2, 3, Kui Zhang 1, 3, Fengfan Yang 1, 3, Xin Zhang 1, 3, Qing Han 1, 3, Zhi-Nan
FcγRIIIA (CD16)-expressing monocytes mediate the depletion of tumor-infiltrating Tregs via ipilimumab-dependent ADCC in melanoma patients
FcγRIIIA (CD16)-expressing monocytes mediate the depletion of tumor-infiltrating Tregs via ipilimumab-dependent ADCC in melanoma patients Emanuela Romano Department of Oncology University of Lausanne and
Understanding and overcoming immunoregulatory barriers within
Understanding and overcoming immunoregulatory barriers within the tumor microenvironment Thomas F. Gajewski, M.D., Ph.D. Professor, Departments of Pathology and Medicine Program Leader, Immunology and
Supplementary Fig. 1 p38 MAPK negatively regulates DC differentiation. (a) Western blot analysis of p38 isoform expression in BM cells, immature DCs
Supplementary Fig. 1 p38 MAPK negatively regulates DC differentiation. (a) Western blot analysis of p38 isoform expression in BM cells, immature DCs (idcs) and mature DCs (mdcs). A myeloma cell line expressing
Index. neurosurgery.theclinics.com. Note: Page numbers of article titles are in boldface type.
Index Note: Page numbers of article titles are in boldface type. A A Complimentary Trial of an Immunotherapy Vaccine Against Tumor-specific EGFRvIII (ACTIVATE), 90 91 Active immunotherapy, 5 8, 96. See
Human and mouse T cell regulation mediated by soluble CD52 interaction with Siglec-10. Esther Bandala-Sanchez, Yuxia Zhang, Simone Reinwald,
Human and mouse T cell regulation mediated by soluble CD52 interaction with Siglec-1 Esther Bandala-Sanchez, Yuxia Zhang, Simone Reinwald, James A. Dromey, Bo Han Lee, Junyan Qian, Ralph M Böhmer and Leonard
Effector T Cells and
1 Effector T Cells and Cytokines Andrew Lichtman, MD PhD Brigham and Women's Hospital Harvard Medical School 2 Lecture outline Cytokines Subsets of CD4+ T cells: definitions, functions, development New
Regulating the Regulators for Cancer Immunotherapy: LAG-3 Finally Catches Up. Drew Pardoll Sidney Kimmel Cancer Center Johns Hopkins
Regulating the Regulators for Cancer Immunotherapy: LAG-3 Finally Catches Up Drew Pardoll Sidney Kimmel Cancer Center Johns Hopkins The hostile immune microenvironment within a tumor Stat3 Stat3 NK Lytic
Tim-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
This is a repository copy of Programmed death 1 expressing regulatory T cells in vitiligo.
This is a repository copy of Programmed death 1 expressing regulatory T cells in vitiligo. White Rose Research Online URL for this paper: http://eprints.whiterose.ac.uk/85671/ Article: Kemp, E.H. (2015)
T Cell Activation, Costimulation and Regulation
1 T Cell Activation, Costimulation and Regulation Abul K. Abbas, MD University of California San Francisco 2 Lecture outline T cell antigen recognition and activation Costimulation, the B7:CD28 family
Immunotherapeutic barriers at the level of the tumor microenvironment Thomas F. Gajewski, M.D., Ph.D.
Immunotherapeutic barriers at the level of the tumor microenvironment Thomas F. Gajewski, M.D., Ph.D. Professor, Departments of Pathology and Medicine Program Leader, Immunology and Cancer Program of the
Nivolumab in Hodgkin Lymphoma
Nivolumab in Hodgkin Lymphoma Stephen M. Ansell, MD, PhD Professor of Medicine Chair, Lymphoma Group Mayo Clinic Conflicts of Interest Research Funding from Bristol Myers Squibb Celldex Therapeutics Seattle
Immunology. T-Lymphocytes. 16. Oktober 2014, Ruhr-Universität Bochum Karin Peters,
Immunology T-Lymphocytes 16. Oktober 2014, Ruhr-Universität Bochum Karin Peters, karin.peters@rub.de The role of T-effector cells in the immune response against microbes cellular immunity humoral immunity
Antiangiogenesis - Immune Therapy Combinations. George Coukos, MD, PhD Heinz Zwierzina, MD
Antiangiogenesis - Immune Therapy Combinations George Coukos, MD, PhD Heinz Zwierzina, MD Overview Effect of VEGF on antitumor immune response Antigen presentation Effector mechanisms Ying and yang and
Allergy and Immunology Review Corner: Chapter 13 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD.
Allergy and Immunology Review Corner: Chapter 13 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD. Chapter 13: Mechanisms of Immunity to Viral Disease Prepared by
Immune surveillance hypothesis (Macfarlane Burnet, 1950s)
TUMOR-IMMUNITÄT A.K. Abbas, A.H. Lichtman, S. Pillai (6th edition, 2007) Cellular and Molecular Immunology Saunders Elsevier Chapter 17, immunity to tumors Immune surveillance hypothesis (Macfarlane Burnet,
Dendritic Cells Loaded with Pancreatic Cancer Stem Cells (CSCs) Lysates Induce Antitumor Immune Killing Effect In Vitro
RESEARCH ARTICLE Dendritic Cells Loaded with Pancreatic Cancer Stem Cells (CSCs) Lysates Induce Antitumor Immune Killing Effect In Vitro Tao Yin 1 *, Pengfei Shi 1, Shanmiao Gou 1, Qiang Shen 2, Chunyou
IMMUNOTHERAPY FOR CANCER A NEW HORIZON. Ekaterini Boleti MD, PhD, FRCP Consultant in Medical Oncology Royal Free London NHS Foundation Trust
IMMUNOTHERAPY FOR CANCER A NEW HORIZON Ekaterini Boleti MD, PhD, FRCP Consultant in Medical Oncology Royal Free London NHS Foundation Trust ASCO Names Advance of the Year: Cancer Immunotherapy No recent
DNA vaccine, peripheral T-cell tolerance modulation 185
Subject Index Airway hyperresponsiveness (AHR) animal models 41 43 asthma inhibition 45 overview 41 mast cell modulation of T-cells 62 64 respiratory tolerance 40, 41 Tregs inhibition role 44 respiratory
Melanoma gene expression profiles to identify mechanisms of tumor resistance
Melanoma gene expression profiles to identify mechanisms of tumor resistance Helena Harlin Human Immunologic Monitoring Facility University of Chicago Introduction High frequencies of melanoma antigen-specific
Tumor Associated Macrophages as a Novel Target for Cancer Therapy
Tumor mass Tumor Associated Macrophage Tumor Associated Macrophages as a Novel Target for Cancer Therapy This booklet contains forward-looking statements that are based on Amgen s current expectations
Mechanisms of Cytokine-Induced Glioma Immunosuppression
30 The Open Cancer Immunology Journal, 2010, 3, 30-35 Mechanisms of Cytokine-Induced Glioma Immunosuppression Open Access Alexander Ksendzovsky,1, Roberta P. Glick 2, Paul Polak 3, Maria-Vittoria Simonini
Simultaneous correlation of cytokine production with Treg and Th17 cell proliferation
Simultaneous correlation of cytokine production with Treg and Th17 cell proliferation Jurg Rohrer, PhD Director, R&D BD Biosciences 23-11773-00 For Research Use Only. Not for use in diagnostic or therapeutic
Immune checkpoint inhibitors in Hodgkin and non-hodgkin Lymphoma: How do they work? Where will we use them? Stephen M. Ansell, MD, PhD Mayo Clinic
Immune checkpoint inhibitors in Hodgkin and non-hodgkin Lymphoma: How do they work? Where will we use them? Stephen M. Ansell, MD, PhD Mayo Clinic Conflicts of Interest Research Funding from Bristol Myers
Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells
Research article Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells Chen Wang, 1 Tai Yi, 1 Lingfeng Qin, 2 Roberto A. Maldonado, 3 Ulrich H. von Andrian, 3
Challenges)facing)An./tumour) Immunotherapy)in)Myeloma)))
Challenges)facing)An./tumour) Immunotherapy)in)Myeloma))) Immune Dysfunction Prof)Gordon)Cook) Leeds)Ins.tute)of)Cancer)&)Pathology) University)of)Leeds) Impaired)immunity)in)MM) )clinical) % of Infection-related
FOCiS. Lecture outline. The immunological equilibrium: balancing lymphocyte activation and control. Immunological tolerance and immune regulation -- 1
1 Immunological tolerance and immune regulation -- 1 Abul K. Abbas UCSF FOCiS 2 Lecture outline Principles of immune regulation Self-tolerance; mechanisms of central and peripheral tolerance Inhibitory
Molecular mechanisms of the T cellinflamed tumor microenvironment: Implications for cancer immunotherapy
Molecular mechanisms of the T cellinflamed tumor microenvironment: Implications for cancer immunotherapy Thomas F. Gajewski, M.D., Ph.D. Professor, Departments of Pathology and Medicine Program Leader,
Diseases 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
5/1/13. The proportion of thymus that produces T cells decreases with age. The cellular organization of the thymus
T cell precursors migrate from the bone marrow via the blood to the thymus to mature 1 2 The cellular organization of the thymus The proportion of thymus that produces T cells decreases with age 3 4 1
Supplementary Figure 1. Normal T lymphocyte populations in Dapk -/- mice. (a) Normal thymic development in Dapk -/- mice. Thymocytes from WT and Dapk
Supplementary Figure 1. Normal T lymphocyte populations in Dapk -/- mice. (a) Normal thymic development in Dapk -/- mice. Thymocytes from WT and Dapk -/- mice were stained for expression of CD4 and CD8.
CRIPTO-1 A POSSIBLE NEW BIOMARKER IN GLIOBLASTOMA MULTIFORME PIA OLESEN, MD, PHD STUDENT
CRIPTO-1 A POSSIBLE NEW BIOMARKER IN GLIOBLASTOMA MULTIFORME PIA OLESEN, MD, PHD STUDENT Glioblastoma WHO Grade IV Glioma Heterogenic Undiffenrentiated phenotype 50% of all Gliomas Around 600 patients
Self Tolerance and MHC Restriction. Dr. Issa Abu-Dayyeh
Self Tolerance and MHC Restriction Dr. Issa Abu-Dayyeh How do we teach B and T cells not to recognise self antigens as dangerous? How do we restrict T cells to recognise only Ags presented on a self MHC
Altered regulatory T cell homeostasis in patients with CD4 + lymphopenia following allogeneic hematopoietic stem cell transplantation
Altered regulatory T cell homeostasis in patients with CD4 + lymphopenia following allogeneic hematopoietic stem cell transplantation Ken-ichi Matsuoka,, Robert J. Soiffer, Jerome Ritz J Clin Invest. 2010;120(5):1479-1493.
5% 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
Immunotherapy for Malignant Brain Cancer: Overcoming Immune Suppression to Improve the Clinical Experience
Immunotherapy for Malignant Brain Cancer: Overcoming Immune Suppression to Improve the Clinical Experience Derek Wainwright, PhD Assistant Professor Departments of Neurological Surgery, Microbiology-Immunology
Cancer Biometrics: Results of the 2003 isbtc Workshop. Theresa L. Whiteside, Ph.D., ABMLI University of Pittsburgh Cancer Institute
Cancer Biometrics: Results of the 2003 isbtc Workshop Theresa L. Whiteside, Ph.D., ABMLI University of Pittsburgh Cancer Institute The workshop objective The objective was to consider state-of-theart approaches
Novel strategies for enhancing the efficacy of therapeutic immunization against cancer Draghiciu, Oana
University of Groningen Novel strategies for enhancing the efficacy of therapeutic immunization against cancer Draghiciu, Oana IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's
2/16/2018. 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
Supplemental Table I.
Supplemental Table I Male / Mean ± SEM n Mean ± SEM n Body weight, g 29.2±0.4 17 29.7±0.5 17 Total cholesterol, mg/dl 534.0±30.8 17 561.6±26.1 17 HDL-cholesterol, mg/dl 9.6±0.8 17 10.1±0.7 17 Triglycerides,
CELLULAR 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
S. No Topic Class No Date
S. No Topic Class No Date 1 Introduction 2 3 4 5 6 7 Fundamentals of Immunology Definitions and basic terms Types of immunity Organs of immune system Cells of immune system Innate immunity PAMPs PRRs Phagocytosis
Supplementary Figure Legends. group) and analyzed for Siglec-G expression utilizing a monoclonal antibody to Siglec-G (clone SH2.1).
Supplementary Figure Legends Supplemental Figure : Naïve T cells express Siglec-G. Splenocytes were isolated from WT B or Siglec-G -/- animals that have not been transplanted (n= per group) and analyzed
Control of intestinal inflammation by regulatory T cells
Control of intestinal inflammation by regulatory T cells Fiona Powrie Sir William Dunn School of Pathology University of Oxford fiona.powrie@path.ox.ac.uk Regulatory T cells prevent immune pathology in
International Society of Breast Pathology. Immune Targeting in Breast Cancer. USCAP 2017 Annual Meeting
International Society of Breast Pathology USCAP 2017 Annual Meeting Immune Targeting in Breast Cancer Ashley Cimino-Mathews, MD Assistant Professor of Pathology and Oncology The Johns Hopkins Hospital
Immune Reconstitution Following Hematopoietic Cell Transplant
Immune Reconstitution Following Hematopoietic Cell Transplant Patrick J. Kiel, PharmD, BCPS, BCOP Clinical Pharmacy Specialist Indiana University Simon Cancer Center Conflicts of Interest Speaker Bureau
Neuroimmunology. Innervation of lymphoid organs. Neurotransmitters. Neuroendocrine hormones. Cytokines. Autoimmunity
Neuroimmunology Innervation of lymphoid organs Neurotransmitters Neuroendocrine hormones Cytokines Autoimmunity CNS has two ways of contacting and regulating structures in the periphery Autonomic
Topic (Final-02): Immunologic Tolerance
Topic (Final-02): Immunologic Tolerance Immunologic tolerance is defined as unresponsiveness to an antigen that is induced by previous exposure to that antigen. The term arose from the experimental observation
Naive, memory and regulatory T lymphocytes populations analysis
Naive, memory and regulatory T lymphocytes populations analysis Jaen Olivier, PhD ojaen@beckmancoulter.com Cellular Analysis application specialist Beckman Coulter France Introduction Flow cytometric analysis
REPROGRAMING IMMUNITY IN RENAL CELL CARCINOMA
REPROGRAMING IMMUNITY IN RENAL CELL CARCINOMA RETHINKING TYROSINE KINASE INHIBITORS Dr. L.M. Antón Aparicio. Complejo Universitario de La Coruña INTRODUCTION Angiogenesis, which is regulated by a fine
Cellular Pathology of immunological disorders
Cellular Pathology of immunological disorders SCBM344 Cellular and Molecular Pathology Witchuda Payuhakrit, Ph.D (Pathobiology) witchuda.pay@mahidol.ac.th Objectives Describe the etiology of immunological
W/T Itgam -/- F4/80 CD115. F4/80 hi CD115 + F4/80 + CD115 +
F4/8 % in the peritoneal lavage 6 4 2 p=.15 n.s p=.76 CD115 F4/8 hi CD115 + F4/8 + CD115 + F4/8 hi CD115 + F4/8 + CD115 + MHCII MHCII Supplementary Figure S1. CD11b deficiency affects the cellular responses
Scott 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 11 T-Cell Activation, Differentiation, and Memory Copyright 2013 by W. H. Freeman and
Discover the PD-1 pathway and its role in cancer 105/15 -ONCO- 07/15
Discover the PD-1 pathway and its role in cancer 105/15 -ONCO- 07/15 Immunology in cancer The role of immunology in cancer Evolving knowledge of the immune system has provided a better understanding of
B6/COLODR/SPL/11C/83/LAP/#2.006 B6/COLODR/SPL/11C/86/LAP/#2.016 CD11C B6/COLODR/SPL/11C/80/LAP/#2.011 CD11C
CD3-specific antibody-induced immune tolerance and suppression of autoimmune encephalomyelitis involves TGF-β production through phagocytes digesting apoptotic T cells Sylvain Perruche 1,3, Pin Zhang 1,
BASIC 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
Supplementary Figure 1
Supplementary Figure 1 Expression of apoptosis-related genes in tumor T reg cells. (a) Identification of FOXP3 T reg cells by FACS. CD45 + cells were gated as enriched lymphoid cell populations with low-granularity.
Timing Matters in T Cell Differentiation
Virtual PI Meeting April 2012 000 p1 001 101 p3 p2 011 100 111 110 Timing Matters in T Cell Differentiation Natasa Miskov-Zivanov University of Pittsburgh 010 Acknowledgements 2 Faeder Lab: Department
The development of T cells in the thymus
T cells rearrange their receptors in the thymus whereas B cells do so in the bone marrow. The development of T cells in the thymus The lobular/cellular organization of the thymus Immature cells are called
Anti-tumor Effects of Activated Human Natural Killer Cells in Orthotopic Human Brain Tumor Models
Anti-tumor Effects of Activated Human Natural Killer Cells in Orthotopic Human Brain Tumor Models William Murphy, PhD Depts. of Dermatology and Internal Medicine Neal Goodwin, PhD Jackson Laboratories
Glioblastoma and CNS tumors
Glioblastoma and CNS tumors PRECEPTORSHIP PROGRAMME IMMUNO-ONCOLOGY Amsterdam, 27 May 2017 Patrick Roth Department of Neurology and Brain Tumor Center University Hospital Zurich Challenges in immunooncology
Disclosure Information. Mary L. Disis
Disclosure Information Mary L. Disis I have the following financial relationships to disclose: Consultant for: VentiRx, Celgene, Emergent, EMD Serono Speaker s Bureau for: N/A Grant/Research support from:
Dendritic cells. Emmanuel STEPHEN-VICTOR (PhD) INSERM U Centre de Recherche des Cordeliers, Paris
Dendritic cells Emmanuel STEPHEN-VICTOR (PhD) INSERM U 1138 - Centre de Recherche des Cordeliers, Paris Pathogens Bacteria, virus, fungi The pathogen-derived antigens need to be transported adptaive immune
Higher frequency of CD4 + CD25 high Treg cells in hemophilia patients with factor VIII inhibitor
Higher frequency of CD4 + CD25 high Treg cells in hemophilia patients with factor VIII inhibitor K.Y. Ding, W.C. Ji, J.S. Wu, T. Li and Y.Y. Sheng Anhui Provincial Hospital Affiliated, Anhui Medical University,