Cancer Immunotherapy: Immune Suppression and Tumor Growth
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Table of contents
- Title Pageiii
- Copyright pageiv
- Table of contentsv
- Contributorsxi
- PART I: PRINCIPLES OF CANCER IMMUNOBIOLOGY1
- CHAPTER 1: Introduction3
- I. OVERVIEW3
- II. HISTORICAL BACKGROUND3
- III. LOOKING AHEAD: MARRYING CHEMOTHERAPY AND IMMUNOTHERAPY5
- IV. PARTS OF THE BOOK6
- References8
- Further Reading8
- CHAPTER 2: Cancer Immunoediting: From Immune Surveillance to Immune Escape9
- I. INTRODUCTION10
- II. CANCER IMMUNE SURVEILLANCE10
- III. CANCER IMMUNOEDITING19
- IV. CONCLUDING REMARKS25
- References25
- CHAPTER 3: Immunosurveillance: Innate and Adaptive Antitumor Immunity29
- I. INTRODUCTION30
- II. INNATE ANTITUMOR RESPONSES30
- III. INNATE IMMUNE CELLS31
- IV. ADAPTIVE ANTITUMOR RESPONSES33
- V. THE INTERPLAY OF INNATE AND ADAPTIVE ANTITUMOR IMMUNITY38
- VI. CONCLUSION39
- References39
- CHAPTER 4: Cytokine Regulation of Immune Tolerance to Tumors43
- I. INTRODUCTION43
- II. CYTOKINE REGULATION OF IMMUNE TOLERANCE TO TUMORS45
- III. SUMMARY AND FUTURE PERSPECTIVES55
- References56
- CHAPTER 5: Immunological Sculpting: Natural Killer Cell Receptors and Ligands63
- I. INTRODUCTION64
- II. ACTIVATING HUMAN NK RECEPTORS65
- III. INHIBITORY NK RECEPTORS72
- IV. THE LY49 RECEPTOR FAMILY74
- V. IMMUNOTHERAPY APPROACHES74
- VI. CONCLUSION77
- References78
- Further Reading80
- CHAPTER 6: Immune Escape: Immunosuppressive Networks83
- I. INTRODUCTION83
- II. IMBALANCE BETWEEN MATURE DCs AND IMMATURE DCs84
- III. IMBALANCE BETWEEN STIMULATORY AND INHIBITORY B7 FAMILY MOLECULES87
- IV. IMBALANCE BETWEEN REGULATORY T CELLS AND CONVENTIONAL T CELLS90
- V. CONCLUDING REMARKS92
- References92
- PART II: CANCER THERAPEUTICS99
- CHAPTER 7: Cytotoxic Chemotherapy in Clinical Treatment of Cancer101
- I. INTRODUCTION101
- II. DNA-DAMAGING AGENTS103
- III. ANTIMETABOLITES109
- IV. ANTIMITOTICS112
- V. CHEMOTHERAPY REGIMENS113
- References115
- Useful Web Sites116
- CHAPTER 8: Targeted Therapeutics in Cancer Treatment117
- I. INTRODUCTION118
- II. CELL CYCLE119
- III. THE MAPK FAMILY131
- IV. CHALLENGES IN THE CLINICAL DEVELOPMENT OF SIGNAL TRANSDUCTION INHIBITORS136
- References140
- CHAPTER 9: Concepts in Pharmacology and Toxicology149
- I. INTRODUCTION150
- II. CONCEPTS IN PHARMACOKINETICS151
- III. CONCEPTS IN TOXICOLOGY159
- IV. CLINICAL CONCERNS FOR PHARMACOLOGY AND SAFETY164
- V. CONCLUSION165
- References165
- Further Reading166
- CHAPTER 10: Cancer Immunotherapy: Challenges and Opportunities167
- I. INTRODUCTION168
- II. PREREQUISITES FOR EFFECTIVE CANCER IMMUNOTHERAPY: IDENTIFYING TUMOR ANTIGENS168
- III. ADOPTIVE (PASSIVEŽ) IMMUNOTHERAPY169
- IV. ACTIVE-SPECIFIC IMMUNOTHERAPY: VACCINES171
- V. CANCER-INDUCED IMMUNOSUPPRESSION IMPINGES ON IMMUNOTHERAPY172
- VI. CANCER IMMUNOTHERAPY IN MICE VERSUS HUMANS175
- VII. IMMUNOTHERAPY AND CANCER STEM CELLS176
- VIII. AUTOIMMUNITY RESULTING FROM CANCER IMMUNOTHERAPY176
- IX. CONCLUSION AND FUTURE CONSIDERATIONS177
- References178
- CHAPTER 11: Cancer Vaccines183
- I. INTRODUCTION184
- II. TUMOR ANTIGENS185
- III. SPONTANEOUS IMMUNITY TO CANCER187
- IV. TOLERAGENIC PRESSURE ON IMMUNITY TO CANCER187
- V. IMMUNE RESPONSES TO CONVENTIONAL VACCINES189
- VI. CANCER VACCINE STRATEGIES194
- VII. DNA VACCINES195
- VIII. CHALLENGES OF TRANSLATION TO THE CLINIC199
- IX. CONCLUDING REMARKS200
- References200
- Further Reading204
- PART III: TARGETS AND TACTICS TO IMPROVE CANCER IMMUNOTHERAPY BY DEFEATING IMMUNE SUPPRESSION205
- CHAPTER 12: Immunotherapy and Cancer Therapeutics: Why Partner?207
- I. INTRODUCTION: WHY IMMUNOTHERAPY FOR CANCER?208
- II. IMMUNE TOLERANCE AND SUPPRESSION: MULTIPLE LAYERS OF NEGATIVE CONTROL209
- III. T CELL ACTIVATION: A RHEOSTAT FOR TUNING IMMUNE RESPONSES212
- IV. IMMUNE MODULATION WITH THERAPEUTIC MONOCLONAL ANTIBODIES219
- V. THERAPEUTICS THAT MITIGATE THE INFLUENCE OF CD4+CD25+ TREGS222
- VI. ENDOCRINE AND BIOLOGICALLY TARGETED THERAPY224
- VII. CONCLUSION225
- References225
- CHAPTER 13: Immune Stimulatory Features of Classical Chemotherapy235
- I. INTRODUCTION236
- II. TUMOR CELL DEATH236
- III. PATHWAYS TO IMMUNOGENICITY239
- IV. CHEMOTHERAPY AND THE IMMUNE SYSTEM243
- V. A PRACTICAL PARTNERSHIP: CHEMOTHERAPY AND IMMUNOTHERAPY246
- VI. EFFECTS OF CHEMOTHERAPY ON HUMAN ANTITUMOR IMMUNITY AND CHEMOIMMUNOTHERAPY CLINICAL TRIALS250
- References252
- CHAPTER 14: Dendritic Cells and Coregulatory Signals: Immune Checkpoint Blockade to Stimulate Immuno257
- I. REGULATION OF T CELL RESPONSES TO ANTIGEN258
- II. REGULATORY T CELLS261
- III. IMMUNE CHECKPOINTS IN THE TUMOR MICROENVIRONMENT262
- IV. MONOCLONAL ANTIBODIES THAT INTERFERE WITH COINHIBITORY RECEPTORS ON T CELLS266
- V. WHAT IS THE MOST EFFECTIVE WAY TO USE CHECKPOINT INHIBITORS?269
- References270
- CHAPTER 15: Regulatory T cells in Tumor Immunity: Role of Toll-Like Receptors277
- I. INTRODUCTION278
- II. IMMUNE CELLS IN IMMUNOSURVEILLANCE AND TUMOR DESTRUCTION278
- III. TLRs AND THEIR SIGNALING PATHWAYS279
- IV. TLRs IN INNATE IMMUNITY, INFLAMMATION, AND CANCER DEVELOPMENT280
- V. TUMOR-INFILTRATING IMMUNE CELLS IN THE TUMOR MICROENVIRONMENT281
- VI. MOLECULAR MARKER FOR CD4+ TREGS282
- VII. ANTIGEN SPECIFICITY OF CD4+ TREGS282
- VIII. SUPPRESSIVE MECHANISMS OF TREGS283
- IX. FUNCTIONAL REGULATION OF TREGS AND EFFECTOR CELLS BY TLR SIGNALING283
- X. IMPLICATIONS FOR ENHANCING ANTITUMOR IMMUNITY284
- XI. CONCLUSION285
- References285
- CHAPTER 16: Tumor-Associated Macrophages in Cancer Growth and Progression289
- I. INTRODUCTION289
- II. MACROPHAGE POLARIZATION290
- III. MACROPHAGE RECRUITMENT AT THE TUMOR SITE291
- IV. TAM EXPRESSION OF SELECTED M2 PROTUMORAL FUNCTIONS294
- V. MODULATION OF ADAPTIVE IMMUNITY BY TAMS296
- VI. TARGETING TAMS297
- VII. CONCLUDING REMARKS300
- References302
- CHAPTER 17: Tumor-Associated Myeloid-Derived Suppressor Cells309
- I. INTRODUCTION310
- II. MULTIPLE SUPPRESSIVE MECHANISMS THAT CONTRIBUTE TO IMMUNOSUPPRESSION IN INDIVIDUALS WITH TUMORS310
- III. MDSCs AS A KEY CELL POPULATION THAT MEDIATES TUMOR-INDUCED IMMUNOSUPPRESSION311
- IV. MDSCs’ USE OF MECHANISMS TO MEDIATE EFFECTS ON MULTIPLE TARGET CELLS317
- V. MDSC INDUCTION BY TUMOR-DERIVED CYTOKINES AND GROWTH FACTORS321
- VI. MDSC LINKING OF INFLAMMATION AND TUMOR PROGRESSION322
- VII. AGENTS RESPONSIBLE FOR REDUCING MDSC LEVELS323
- VIII. CONCLUSIONS: IMPLICATIONS FOR IMMUNOTHERAPY326
- References327
- Further Reading331
- CHAPTER 18: Programmed Death Ligand-1 and Galectin-1: Pieces in the Puzzle of Tumor-Immune Escape333
- I. PROGRAMMED DEATH LIGAND 1 AND PROGRAMMED DEATH 1 INTERACTIONS334
- II. GALECTIN 1338
- References344
- Further Reading346
- CHAPTER 19: Indoleamine 2,3-Dioxygenase in Immune Escape: Regulation and Therapeutic Inhibition347
- I. INTRODUCTION348
- II. IDO FUNCTION IN T CELL REGULATION351
- III. COMPLEX CONTROL OF IDO BY IMMUNE REGULATORY FACTORS351
- IV. IMMUNE TOLERANCE VIA IDO IN DENDRITIC CELLS353
- V. IDO DYSREGULATION IN CANCER CELLS357
- VI. IDO AS A TARGET FOR THERAPEUTIC INTERVENTION359
- VII. DISCOVERY AND DEVELOPMENT OF IDO INHIBITORS360
- VIII. CONCLUSION361
- References362
- Further Reading368
- CHAPTER 20: Arginase, Nitric Oxide Synthase, and Novel Inhibitors of L-Arginine Metabolism in Immune369
- I. INTRODUCTION370
- II. NOS: GENES, REGULATION, AND ACTIVITY371
- III. ARG: GENES, REGULATION, AND ACTIVITY372
- IV. IMMUNOREGULATORY ACTIVITIES OF ARG AND NOS374
- V. POSSIBLE PHYSIOLOGICAL ROLE FOR L-ARG METABOLISM IN IMMUNITY CONTROL381
- VI. NOS IN CANCER382
- VII. ARG IN CANCER384
- VIII. ARG AND NOS INHIBITORS: A NOVEL CLASS OF IMMUNE ADJUVANTS?386
- IX. CONCLUSION AND PERSPECTIVES388
- References389
- Further Reading399
- Index401
- Color PlateColor plate_1
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 tumoral 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 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.
* 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
* 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