Cancer Immunotherapy

Cancer Immunotherapy

Immune Suppression and Tumor Growth

2nd Edition - June 4, 2013

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  • Editors: George Prendergast, Elizabeth Jaffee
  • Hardcover ISBN: 9780123942968
  • eBook ISBN: 9780123946331

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There has been major growth in understanding immune suppression mechanisms and its relationship to cancer progression and therapy. This book highlights emerging new principles of immune suppression that drive cancer, and it offers radically new ideas about how therapy can be improved by attacking these principles. Following work that firmly establishes immune escape as an essential trait of cancer, recent studies have now defined specific mechanisms of tumor immune suppression. It also demonstrates how attacking tumors with molecular targeted therapeutics or traditional chemotherapeutic drugs can produce potent anti-tumor effects in preclinical models. This book provides basic, translational, and clinical cancer researchers with an indispensable overview of immune escape as a critical trait in cancer and how applying specific combinations of immunotherapy and chemotherapy to attack this trait may radically improve the treatment of advanced disease.

Key Features

  • Offers a synthesis of concepts that are useful to cancer immunologists and pharmacologists, who tend to work in disparate fields with little cross-communication
  • Drs. Prendergast and Jaffee are internationally recognized leaders in cancer biology and immunology who have created a unique synthesis of fundamental and applied concepts in this important new area of cancer research
  • Summarizes the latest insights into how immune escape defines an essential trait of cancer
  • Includes numerous illustrations, including how molecular-targeted therapeutic drugs or traditional chemotherapy can be combined with immunotherapy to improve anti-tumor efficacy and how reversing immune suppression by the tumor can cause tumor regression


Basic, translational, and clinical cancer researchers as well as practicing oncologists and their patients

Table of Contents

  • List of Contributors

    Chapter 1. Introduction


    I Summary

    II Historical Background

    III The Challenge of Cancer

    IV Parts of the Book


    Section 1: Principles of Basic Immunology

    Chapter 2. Components of the Immune System

    I Overview

    II Principal Tissues and Organs

    III Cells of the Immune System

    IV Immune Responses

    V Lymphocyte Recognition of Antigen

    VI Effector Functions


    Chapter 3. Adaptive Immunity: B Cells and Antibodies

    I Introduction to B Cells

    II B-Cell Development

    III Mature B Cells

    IV Antibody Function

    V B Cells and Cancer

    VI Conclusions


    Chapter 4. Adaptive Immunity: T Cells and Cytokines

    I An Overview of the Events That Initiate an Adaptive Immune Response

    II T-cell Activation: A Deeper Look

    III The Differentiation of Naïve T Cells into Effector T Cells

    IV The Significance of Polarizing Cytokines

    V CD8+ T Cells Develop into Cytotoxic Lymphocytes

    VI The Activities of Effector and Memory T Cells in Tissues

    VII Two Major Types of Memory T Cells Remain after Antigen is Cleared

    VIII The Challenges Faced by the Adaptive Immune System When Responding to Tumors

    Further Reading

    Chapter 5. Dendritic Cells: Antigen Processing and Presentation

    I Dendritic Cells: Introduction

    II Antigen Processing and Presentation

    III MHC Class I

    IV MHC Class II

    V Alternate Pathways of Antigen Presentation

    VI Dendritic Cell Subsets and Specialized Functions

    VII Human DC Subsets

    VIII Conclusions


    Chapter 6. Mucosal Immunity

    I Overview

    II Mucosal Surfaces are the Major Portals of Entry for Antigen

    III Epithelial Barrier

    IV Inductive and Effector Sites in the Mucosa-associated Lymphoid Tissue

    V The Microbiome and Mucosal Surfaces

    VI Tolerance to Dietary Antigen and the Microbiome


    Section 2: Principles of Cancer Immunobiology

    Chapter 7. Cancer Immunoediting: From Surveillance to Escape


    I Introduction

    II History of Cancer Immune Surveillance and Cancer Immunoediting

    III Mouse Models of Cancer Used in the Establishment of the Three ES

    IV Cancer Immunoediting in Humans


    Chapter 8. Immunosurveillance: Innate and Adaptive Antitumor Immunity

    I Introduction

    II Innate Antitumor Responses

    III Innate Immune Cells

    IV Adaptive Antitumor Responses

    V Adaptive Immunity in Immunosurveillance

    VI Targets of Antitumor T-Cell Responses

    VII Antitumor Effector Mechanisms: Cytokines

    VIII Antitumor Effector Mechanisms: Cytotoxic Mechanisms

    IX The Interplay of Innate and Adaptive Antitumor Immunity

    X Conclusion


    Chapter 9. Immunological Sculpting: Natural Killer-Cell Receptors and Ligands

    I Introduction

    II NK Education, Licensing, and Priming

    III How Receptor: Ligand Interactions Trigger Cell Lysis

    IV Receptors for MHC I and MHC I-Related Molecules

    V Conclusion


    Chapter 10. Th17 Cells in Cancer

    I Th17 Definition

    II Generation, Cytokine Profile and Genetic Control of Th17 Cells

    III Th17-Cell Plasticity

    IV Th17-Cell Stemness

    V Th17 Cancer Immunity

    VI Th17 Associated Cytokines and Carcinogenesis

    VII Conclusion


    Chapter 11. Immune Escape: Immunosuppressive Networks

    I Introduction

    II Dysfunctional T-Cell Differentiation

    III T-Cell Exhaustion in Cancer

    IV Balance of Extracellular Adenosine and ATP in the Tumor: A Fundamental Regulator of Immune Reactivity

    V Chemical Barriers Faced by T Cells in the Tumor

    VI Conclusions


    Section 3: Introduction to Cancer Therapeutics

    Chapter 12. Principles of Cytotoxic Chemotherapy

    I Introduction

    II Clinical Use of Chemotherapy

    III Tumor Growth and Its Impact on Chemotherapy Use

    IV General Principles of Chemotherapy Use

    V Classes of Chemotherapies and Their Function

    VI Conclusions


    Chapter 13. Pharmacokinetics and Safety Assessment

    I Introduction

    II Concepts in Pharmacokinetics (PK)

    III Concepts in Toxicology

    IV Clinical Concerns for Pharmacology and Safety

    V Conclusions


    Chapter 14. Monoclonal Antibodies for Cancer Therapy and Prevention: Paradigm Studies in Targeting the neu/ERBB2/HER2 Oncoprotein


    I Introduction

    II ERBB2/HER2/NEU in Human Disease

    III ERBB2/NEU as a Therapeutic Target

    IV Conclusions


    Chapter 15. Genetic Vaccines against Cancer: Design, Testing and Clinical Performance


    I Introduction

    II DNA Vaccines

    III Messenger RNA Vaccines

    IV Virus-like Particle Vaccines

    V Plant Viral Particles and Their Derivatives as Vaccines

    VI PVX-based Plant Viral Particle (PVP) Conjugate Vaccines

    VII Vaccination of Human Subjects

    VIII Quantitative and Qualitative Features of Vaccine-induced T-cell Responses

    IX Clinical Trials of DNA Vaccines

    X Immune Responses to DNA Vaccination

    XI Immunotherapy Trial Endpoints and Choice of Clinical Settings

    XII Immunological Assay Harmonization


    Chapter 16. Comprehensive Immunomonitoring to Guide the Development of Immunotherapeutic Products for Cancer

    I Immunotherapy of Cancer

    II Immunomonitoring

    III Monitoring of Unwanted Immune Reactions

    IV Harmonization of Immune Monitoring

    V Immunoguiding


    Section 4: Strategies of Passive and Active Immunotherapy

    Chapter 17. Adoptive T-cell Therapy: Engineering T-cell Receptors

    I Early Trials of Adoptive T-cell Therapy

    II Isolating TCRs for Gene Transfer

    III Antigen Choice for TCR Therapy

    IV Engineering to Improve TCR Activity

    V TCR Delivery

    VI Clinical Trials

    VII Overcoming Tumor Microenvironment Inhibition of T-Cell Function

    VIII Conclusion


    Chapter 18. Dendritic Cell Vaccines: Sipuleucel-T and Other Approaches


    I Generating a Cancer Vaccine

    II Dendritic Cells: Critical for Generating an Immune Response

    III History and Basic Biology of DC Vaccines∗∗

    IV Sipuleucel-T: A Dendritic Cell Vaccine for Prostate Cancer

    V Improving DC Vaccines

    VI Improving DC Vaccines: Combination Treatment Approaches

    VII Immune Checkpoint Blockade

    VIII Selected DC Vaccines in Clinical Development

    IX Conclusion



    Chapter 19. Antibodies to Stimulate Host Immunity: Lessons from Ipilimumab

    I Introduction

    II Preclinical Development of CTLA-4 Blockade

    III Clinical Development of Ipilimumab

    IV Lessons Learned during the Clinical Development of Ipilimumab

    V Clinical Testing of Ipilimumab in Diseases Other Than Melanoma

    VI Outstanding Questions and Future Directions

    VII Conclusions


    Chapter 20. Recombinant TRICOM-based Therapeutic Cancer Vaccines: Lessons Learned

    I The Choice of Recombinant Poxviral Vectors

    II Development of Preclinical Models

    III T-Cell Co-stimulation: Development of Tricom Vectors

    IV Clinical Trials

    V The Importance of Clinical Trial Design in Vaccine Therapy

    VI Prostate Cancer Clinical Trials

    VII Tricom Vaccines also Contain Tumor Antigen Agonist Epitopes

    VIII Tricom Vaccination Affects Tumor Growth Rates

    IX Intratumoral Vaccination: Clinical Studies

    X Combination Therapies—Preclinical Studies

    XI Combination Therapies—Clinical Studies

    XII Lessons Learned and Moving Forward


    Chapter 21. Adjuvant Strategies for Vaccines: The Use of Adjuvants within the Cancer Vaccine Setting

    I Introduction

    II Why Adjuvants Work

    III Tumor-associated Antigens and the Need for Adjuvants in Cancer Vaccines

    IV Immunostimulatory Adjuvants

    V Particulate vaccine adjuvants

    A Emulsions

    VI Dc Priming in Vivo Versus Ex Vivo

    VII Conclusions


    Section 5: Improving Immunotherapeutic Responses

    Chapter 22. Epigenetic Approaches: Emerging Role of Histone Deacetylase Inhibitors in Cancer Immunotherapy

    I Introduction

    II Tumor-Induced Tolerance is a Significant Barrier for Cancer Immunotherapy

    III Epigenetics and Cancer

    IV Role of Specific HDACs in Immunity: Molecular Signaling and Pathways

    V HDIs

    VI Controversy: Are HDIs Pro- or Anti-Inflammatory Drugs?

    VII Conclusions


    Chapter 23. Molecular Profiling of Immunotherapeutic Resistance


    I Introduction—The Bedside to Bench and Back (BB&B) approach to tumor immunology: In Vivo Veritas

    II Strategies to Identify Molecular Pathways Associated With Immunoresponsiveness and Immunoresistance Following Immunotherapy

    III The Emerging of a More Falsifiable, Informative and Preferred Theory: The Immunologic Constant of Rejection (ICR)

    IV Understanding the Mechanism of Actions of Immunotherapeutic Agents through Gene Expression Profiling

    V Understanding the Immune-Mediated Tumor Rejection through Gene Expression Profiling

    VI Predicting Immune Responsiveness to Immunotherapeutics Through Gene Expression Profiling

    VII Linkage Between Autoimmunity and Tumor Rejection

    VIII Understanding the Origin of the Immune-Signature and Future Directions

    IX Conclusion


    Chapter 24. Immune Stimulatory Features of Classical Chemotherapy


    I Introduction

    II The Immunopotentiating Effect of Cancer Chemotherapy

    III How Can We Use and Enforce the Immunogenic Properties of Chemotherapeutic Drugs?

    IV Conclusions


    Chapter 25. Immunotherapy and Cancer Therapeutics: A Rich Partnership


    I Introduction: Why Integrate Cancer Drugs with Tumor Immunotherapy?

    II Chemotherapy and Tumor Immunity

    III Clinical Trials of Chemoimmunotherapy

    IV Immune Modulation with Therapeutic Monoclonal Antibodies

    V Immune Modulation with Biologically Targeted Therapy

    VI Conclusions

    Conflict of Interest


    Section 6: Targeting Strategies to Defeat Immune Suppression

    Chapter 26. JAK/STAT Signaling in Myeloid Cells: Targets for Cancer Immunotherapy

    I Introduction

    II Overview of JAK/STAT Signaling

    III JAK/STAT3 Signaling in Myeloid Cell-Mediated Immunosuppression

    IV Targeting JAK/STAT3 Signaling in Myeloid Cells

    V Concluding Remarks


    Chapter 27. Tumor-associated Macrophages in Cancer Growth and Progression


    I Introduction

    II Macrophage Polarization

    III Macrophage Recruitment at the Tumor Site

    IV Tam Express Selected M2 Protumoral Functions

    V Modulation of Adaptive Immunity by TAM

    VI Targeting TAM

    VII Concluding Remarks


    Chapter 28. Tumor-induced Myeloid-derived Suppressor Cells


    I Introduction

    II Mouse and Human MDSC are a Heterogeneous Mixture of Immature Myeloid Cells

    III MDSC use Diverse Suppressive Mechanisms to Inhibit Antitumor Immunity

    IV Inflammation Drives MDSC Accumulation and Suppression

    V MDSC Turnover

    VI Therapeutic Approaches for Reducing MDSC-Mediated Immune Suppression

    VII Conclusions


    Chapter 29. HyperAcute Vaccines: A Novel Cancer Immunotherapy


    I Background and Historical Perspective

    II Preclinical Development of Hyperacute® Immunotherapy

    III Clinical Development of HyperAcute Immunotherapy

    IV Conclusions


    Chapter 30. Tumor Exosomes and Their Impact on Immunity and Cancer Progression

    I Introduction

    II Discovery and Definition of Exosomes

    III Biogenesis and Composition of Exosomes from Normal and Tumor Cells

    IV Separation and Handling of Exosomes

    V Immunosuppressive Role of Tumor Exosomes

    VI Role of Tumor-derived Exosomes in Cancer Progression

    VII Mechanisms of Interaction with Target Cells

    VIII Tumor-derived Exosomes and Cancer Therapies

    IX Tumor-derived Exosomes as Diagnostic Agents

    X Conclusion and Future Needs


    Chapter 31. Galectins: Key Players in the Tumor Microenvironment


    I Galectins: Definition, Structure and Function

    II Galectin–Glycan Interactions as Key Modulators of Tumor Immunity

    III Galectins in the Tumor Microenvironment: Non-Immune Related Functions

    IV Emerging Roles of Galectins in Tumor Chemoresistance

    V Galectin Inhibitors as Potential Anticancer Agents

    VI Conclusions

    Conflict of Interest


    Chapter 32. IDO in Immune Escape: Regulation and Therapeutic Inhibition


    I Introduction

    II Tryptophan Catabolism by IDO: A Historical Conundrum

    III IDO Dysregulation in the pathogenesis of cancer

    IV 1MT as a Therapeutic Prototype

    V Conclusions

    Recommended Resources Websites

    Further Reading


    Chapter 33. IDO Pathway: Effect on Foxp3+ Tregs and Cancer

    I Introduction

    II IDO Is a Natural Mechanism of Peripheral Tolerance

    III IDO Expression in Human Tumors and Tumor-Draining LNs

    IV IDO and Tregs

    V Downstream Mechanisms of IDO

    VI Induction of IDO by Tregs

    VII IDO-Pathway Inhibitor Drugs as a Potential Strategy to Reduce Treg-Mediated Suppression

    Conflict of Interest


    Chapter 34. Arginase, Nitric Oxide Synthase, and Novel Inhibitors of L-arginine Metabolism in Immune Modulation


    I Introduction

    II Nitric Oxide Synthase (NOS): Genes, Regulation, and Activity

    III Arginase (ARG): Genes, Regulation, and Activity

    IV Immunoregulatory Activities of ARG and NOS

    V Mechanisms of NOS-Dependent Immunoregulation

    VI Mechanisms of ARG-Dependent Immunoregulation

    VII ARG and NOS Cooperation in Immunoregulation: An Emerging Concept

    VIII Peroxynitrite Generation

    IX Peroxynitrite and Autoimmunity

    X Hydrogen Peroxide Generation

    XI Is there a Physiological Role for L-Arg Metabolism in the Control of Immunity?

    XII NOS in Cancer

    XIII ARG in Cancer

    XIV ARG and NOS Inhibitors: A Novel Class of Immune Adjuvants?

    XV Conclusions and Perspectives

    Selected Internet URLs




Product details

  • No. of pages: 684
  • Language: English
  • Copyright: © Academic Press 2013
  • Published: June 4, 2013
  • Imprint: Academic Press
  • Hardcover ISBN: 9780123942968
  • eBook ISBN: 9780123946331

About the Editors

George Prendergast

Affiliations and Expertise

Lankenau Institute for Medical Research, Wynnewood, PA, U.S.A.

Elizabeth Jaffee

Affiliations and Expertise

Department of Oncology, SKCCC, Johns Hopkins University, Baltimore, MD, U.S.A.

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