Fast Facts: Immuno-Oncology PDF
Preview Fast Facts: Immuno-Oncology
F A Fill the gap in your knowledge, fast! S T FAST FACTS F with Fast Facts – the ultimate medical handbook series A C T S Immuno-Oncology I m m FAST FACTS u Immuno-Oncology n o - O n 11 Components of the immune system c o l o g 24 How cancers evade the immune system y Stephen Clarke and Bob T Li 35 How cancer immunotherapy works 58 Clinical use of immune checkpoint inhibitors 76 The future of immuno-oncology ISBN 978-1-910797-70-9 From fundamentals to future directions the best offers are on fastfacts.com 9 781910 797709 © 2017 Health Press Ltd. www.fastfacts.com FAST FACTS Fast Facts: Immuno-Oncology Stephen Clarke OAM MBBS PhD MD FRACP FAChPM Director, Area Cancer Services Northern Sydney Local Health District Professor of Medicine, University of Sydney Royal North Shore Hospital New South Wales, Australia Bob T Li MD MPH MBBS FRACP Attending Medical Oncologist Thoracic Oncology and Early Drug Development Service Memorial Sloan Kettering Cancer Center New York, USA Declaration of Independence This book is as balanced and as practical as we can make it. Ideas for improvement are always welcome: [email protected] © 2017 Health Press Ltd. www.fastfacts.com Fast Facts: Immuno-Oncology First published November 2017 Text © 2017 Stephen Clarke, Bob T Li © 2017 in this edition Health Press Limited Health Press Limited, Elizabeth House, Queen Street, Abingdon, Oxford OX14 3LN, UK Tel: +44 (0)1235 523233 Book orders can be placed by telephone or via the website. For regional distributors or to order via the website, please go to: fastfacts.com For telephone orders, please call +44 (0)1752 202301 Fast Facts is a trademark of Health Press Limited. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the express permission of the publisher. The rights of Stephen Clarke and Bob T Li to be identified as the authors of this work have been asserted in accordance with the Copyright, Designs & Patents Act 1988 Sections 77 and 78. The publisher and the authors have made every effort to ensure the accuracy of this book, but cannot accept responsibility for any errors or omissions. For all drugs, please consult the product labeling approved in your country for prescribing information. Registered names, trademarks, etc. used in this book, even when not marked as such, are not to be considered unprotected by law. A CIP record for this title is available from the British Library. ISBN 978-1-910797-70-9 Clarke S (Stephen) Fast Facts: Immuno-Oncology/ Stephen Clarke, Bob T Li Cover image is a conceptual illustration of T cells attacking cancer cells marked by monoclonal antibodies. Evan Oto/Science Photo Library. Medical illustrations by Graeme Chambers. Typesetting by Thomas Bohm, User Design, Illustration and Typesetting, UK. Printed in the UK with Xpedient Print. © 2017 Health Press Ltd. www.fastfacts.com Glossary 5 Introduction 9 Components of the immune system 11 How cancers evade the immune system 24 How cancer immunotherapy works 35 Clinical use of immune checkpoint inhibitors 58 The future of immuno-oncology 76 Useful resources 84 Index 85 © 2017 Health Press Ltd. www.fastfacts.com © 2017 Health Press Ltd. www.fastfacts.com Glossary Abscopal response: a response to BCG: Bacillus Calmette–Guérin – radiotherapy that is achieved at sites an adjuvant used to stimulate an distant from the treatment site immune response in the production of vaccines ACT: adoptive cell transfer – a form of cell-based cancer immunotherapy BCR: B cell receptor in which circulating or tumor- BiTE®: bispecific T-cell engager – infiltrating lymphocytes are collected a chimeric protein consisting of two from the patient, modified ex vivo single-chain variable fragments from as necessary to attack the patient’s separate monoclonal antibodies, one specific neoantigens, and reinfused targeting a tumor-associated antigen, into the patient and the other targeting a T-cell Adaptive (acquired) immunity: surface antigen immunity conferred by the formation CAR-T: chimeric antigen receptor- of antibodies following exposure to expressing T cell – a lymphocyte foreign material (antigens) that has been genetically modified ADCC: antibody-dependent cell- to express a transmembrane protein mediated cytotoxicity – a cell- consisting of the tumor-associated mediated immune mechanism in antigen-binding domain of an which an effector cell of the immune antibody linked to one or more system lyses a target cell, the surface immunostimulatory domains antigens of which have been bound CCL22: a chemokine that promotes by specific antibodies trafficking of regulatory T cells to Adjuvant: a compound that tumor sites augments the immune response CD22: a non-specific receptor to an antigen inhibitor that reduces the activation Anergy: a state of non-activity of B cell receptors induced in maturing lymphocytes CEACAM1: carcinoembryonic following exposure to self-antigens antigen-related cell adhesion Antigen: a substance capable of molecule 1 – an adhesion molecule triggering an immune response by that is expressed by natural killer binding to an antibody cells and T lymphocytes, and is over- expressed in most melanomas APC: antigen-presenting cell Cellular (cell-mediated) immunity: Apoptosis: programmed cell death acquired immune responses mediated by T lymphocytes 5 © 2017 Health Press Ltd. www.fastfacts.com Fast Facts: Immuno-Oncology Chemokine: a cytokine that Dendritome: a fusion between a promotes recruitment of dendritic cell and an inactivated inflammatory or immune cells to cancer cell, which is intended to sites of injury or infection prime immune responses directed against tumor-associated antigens Complement: a cascade of plasma proteins that facilitates EGFR: epidermal growth factor (or ‘complements’) the ability of receptor antibodies to eliminate pathogens Epitope spreading: the acquired CRS: cytokine release syndrome ability of an immunotherapy directed against a specific antigen to react to CSC: cancer stem cell multiple antigens CTLA-4: cytotoxic T-lymphocyte- GM-CSF: granulocyte macrophage associated protein 4 – a protein colony-stimulating factor that plays a key role in deactivated cytotoxic CD8+ T cells through HMGB1: high mobility group binding to CD80 (B7-1) on antigen- box 1 – a damage-associated presenting cells molecular pattern released following immunogenic cell death Cytokines: chemical mediators produced by inflammatory cells at Humoral immunity: acquired sites of infection or injury, which immune responses mediated by trigger further recruitment of B lymphocytes inflammatory cells ICD: immunogenic cell death – a form Cytotoxic (CD8+) T cells: a class of of apoptosis triggered by certain forms T cells (also known as killer T cells) of chemotherapy and radiotherapy that induce the death of damaged IDO: indoleamine 2,3-dioxygenase – cells, such as cells infected with an enzyme that depletes intracellular viruses or other pathogens supplies of tryptophan, which is DAMP: damage-associated molecular needed for T-cell proliferation pattern – a molecule produced in IFN: interferon response to tissue damage that is recognized by immune cells IL: interleukin expressing pattern recognition IMiD: immunomodulatory drug receptors Immune checkpoints: receptor- ligand systems that, when activated, downregulate immune responses to prevent autoimmunity, minimize damage to healthy tissue during an immune response, or both 6 © 2017 Health Press Ltd. www.fastfacts.com Glossary Immune tolerance: a state in which NLR: nucleotide-binding the immune system is unresponsive oligomerization domain-like receptor to a stimulus that would normally –a group of pattern recognition provoke an immune response receptors that play key roles in innate immune responses Immunogenicity: the ability (e.g. of a cancer cell) to trigger an immune NOD: nucleotide-binding response oligomerization domain Innate immunity: immunity nTreg cells: natural regulatory T cells conferred by mechanisms present Opsonization: labeling of pathogens throughout life or other foreign material by enzymes irRC: immune-related response of the complement system, which criteria facilitates phagocytosis by cells of the innate immune system LPS: lipopolysaccharide – an adjuvant used to stimulate an OX40: Tumor necrosis factor receptor immune response in the production superfamily member 4 of vaccines PAMP: pathogen-associated mAb: monoclonal antibody molecular pattern – a molecule secreted by a pathogen, such as MDSC: myeloid-derived suppressor bacterial lipopolysaccharide, which cell – a type of myeloid progenitor is recognized by immune cells immune cell that inhibits immune expressing pattern recognition responses, produces cytokines receptors that promote tumor invasion and metastasis, such as interleukin-6, and PD-1: programmed cell death-1 suppresses T-cell activation (receptor) – an immune checkpoint that plays an important role in MHC: major histocompatibility enabling cancer cells to avoid complex – cell surface proteins detection and elimination by the that bind to antigens and expose immune system them to antigen-presenting cells, thereby facilitating adaptive immune PD-L1: programmed cell death 1 responses receptor ligand Naive T cell: a mature T cell – Pericytes: a specialized mesenchymal developed in the thymus and released cell type related to smooth muscle into the periphery – that has not yet cells, that support the tumor encountered a specific antigen endothelium NK cells: natural killer cells – a type Phagocytosis: ingestion of pathogens of T cell that contributes to innate or other foreign material by cells immune responses such as macrophages, monocytes and neutrophils 7 © 2017 Health Press Ltd. www.fastfacts.com Fast Facts: Immuno-Oncology PRR: pattern recognition receptor TGF-β: transforming growth factor-β –proteins present on the surface –a cytokine that plays an important of inflammatory cells such as role in inducing differentiation of macrophages, which recognize regulatory T cells foreign proteins (collectively known Th: helper T cells as pathogen-associated molecular patterns) TIGIT: T cell immunoreceptor with immunoglobulin and Pseudoprogression: an apparent immunoreceptor tyrosine-based increase in tumor size following the inhibitory domains – an immune start of immunotherapy, caused by receptor present on some T cells and infiltration of reactivated T cells into natural killer cells the tumor, causing inflammation TIL: tumor-infiltrating lymphocyte RECIST: Response Evaluation Criteria in Solid Tumors TLR: toll-like receptor T cells: a type of lymphocyte that TNF: tumor necrosis factor plays a number of key roles in Toll-like receptor ligands: a group immune responses of proteins that play important roles TAA: tumor-associated antigen in antigen recognition by the innate immune system TCR: T cell receptor Teff: effector T cells Treg: regulatory T cells 8 © 2017 Health Press Ltd. www.fastfacts.com Introduction Recent advances in immuno-oncology have revolutionized the treatment of cancer. With treatment aimed at modulating the immune system, some patients with incurable advanced cancers may now experience long-term responses and significantly improved survival. This has led to unprecedented accelerated regulatory approvals, with promising therapies already being incorporated into the current standards of care for many tumor types. Although significant challenges remain and many more questions remain unanswered, the field is expected to move at even faster speed. Today, most oncology professionals need a good understanding of immuno-oncology to practice at the highest level. This includes knowledge of the fundamentals of immunology, cancer immunoediting and the many different types of cancer immunotherapy, including immune checkpoint inhibitors. It is important to grasp the future directions of this evolving field. However, it is difficult to obtain the key facts from the sea of information out there, especially when one has little time. Whether you are a practicing oncologist, an oncology health professional, a medical student, a cancer researcher or industry professional, Fast Facts: Immuno-Oncology provides you with all you need to know about the topic, concisely summarized. The book was especially written so that, after an easy read, you will be well equipped to understand immuno-oncology in the context of your professional work. 9 © 2017 Health Press Ltd. www.fastfacts.com
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