دانلود کتاب CANCER IMMUNOLOGY cancer immunotherapy for organ specific tumors.

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Preface Acknowledgment Contents Abbreviations Contributors 1: Cancer Immunotherapy Confers a Global Benefit 1.1 Introduction 1.2 Incidence, Morbidity, and Mortality of Cancers: Why Is a New Therapeutic Avenue Indicated? 1.2.1 Cancer Incidence 1.2.2 Cancer Mortality Rate 1.3 History of Immunotherapy of Cancers 1.4 Immunotherapy Is Going Upstream to Combat Cancers 1.4.1 Prophylactic Implication of Immunotherapy 1.4.2 Therapeutic Implication of Immunotherapy 1.5 Strategies of Cancer Immunotherapy 1.5.1 Immunotherapy Acts to Eliminate Immunosuppression 1.5.2 Immunotherapy Boosts the Antitumor Immune Responses and Enhances Killing of the Tumor Cell 1.5.2.1 Activated DCs and T Cells Are Pivotal in Cancer Immunotherapy 1.5.2.2 Materials of Activating DCs and T Cells 1.6 At Which Line of Treatment? 1.7 Monotherapy or Combined Therapy? 1.8 Monitoring the Immunological and Clinical Responses to Immunotherapy 1.9 Limitations of Cancer Immunotherapy 1.10 Supportive Therapy 1.11 Effect of Immunotherapy on Health-Related Quality of Life of Cancer Patients 1.12 Cost-Effectiveness of Cancer Immunotherapy 1.13 Concluding Remarks References 2: Immunotherapy for Pediatric Solid Tumors 2.1 Introduction 2.2 Solid Tumors 2.2.1 Sarcomas 2.2.1.1 Osteosarcoma 2.2.1.2 Ewing Sarcoma 2.2.1.3 Soft-Tissue Sarcomas Rhabdomyosarcoma Non-rhabdomyosarcoma Soft-Tissue Sarcomas 2.2.2 Neuroblastoma 2.2.3 Nephroblastoma 2.2.4 Hepatoblastoma 2.2.5 Systemic Germ Cell Tumors 2.2.6 Central Nervous System Tumors 2.2.6.1 Embryonal Tumors Medulloblastoma CNS Primitive Neuroectodermal Tumors Atypical Teratoid/Rhabdoid Tumors 2.2.6.2 Gliomas Low-Grade Gliomas High-Grade Gliomas Brainstem Gliomas Ependymomas 2.2.6.3 Pineal Region Tumors 2.2.7 Retinoblastoma 2.3 Immune Therapy and Pediatric Solid Tumors 2.3.1 Tumor-Targeting Monoclonal Antibodies (mAbs) 2.3.1.1 Cell Surface Immune Targets Gangliosides B7-H3 RANK-L 2.3.1.2 Growth Factor Receptors and Oncogenes HER2 Insulin-Like Growth Factor-1 Receptors Epidermal Growth Factor Receptor Family Platelet-Derived Growth Factor Vascular Endothelial Growth Factor 2.3.1.3 Immunomodulatory Monoclonal Antibodies Cytotoxic T Lymphocyte Antigen 4 and Programmed Death Receptor 1 2.3.2 Adoptive Cell Transfer 2.3.3 Anticancer Vaccines 2.3.3.1 Peptide-Based Vaccines 2.3.3.2 Dendritic Cell-Based Vaccines 2.3.3.3 Genetically Modified Tumor Vaccines 2.3.3.4 Other Adoptive Cell Therapies 2.4 Concluding Remarks References 3: Immunotherapeutic Strategies for Multiple Myeloma 3.1 Introduction 3.2 Immune Therapy for Myeloma: Overcoming Tumor-Associated Immune Suppression 3.3 Antibody-Mediated Strategies 3.3.1 CS1 3.3.2 CD38 3.3.3 PD-1/PD-L1 3.3.4 Antibody Conjugates and Bispecific Antibodies 3.4 Cellular Immunotherapy for Multiple Myeloma 3.4.1 Allogeneic Transplantation 3.4.2 Myeloma Vaccines 3.4.2.1 Peptide-Based Myeloma Vaccines 3.4.2.2 Cell-Based Myeloma Vaccines 3.4.3 Adoptive Cell Therapy 3.4.3.1 Marrow-Infiltrating T Cells 3.4.3.2 NK Cell Therapy 3.4.4 Engineered T Cells 3.4.4.1 TCR T Cells 3.4.4.2 CAR T Cells 3.5 Concluding Remarks References 4: Immunopathology and Immunotherapy of Myeloid Leukemia 4.1 Introduction 4.2 Immunopathology of Acute Myeloid Leukemia 4.2.1 Causes of Genetic Alterations 4.2.1.1 Primary AML 4.2.1.2 Secondary AML Acute Myeloid Leukemia with Myelodysplasia-Related Changes (AML-MDS) Therapy-Related Myeloid Neoplasms (t-AML) 4.2.2 Genes Affected in AML 4.2.3 Models for Leukemogenesis Through Gene Alterations 4.2.4 The Leukemic Stem Cell 4.2.4.1 Phenotype of the LSC 4.2.4.2 Clinical Relevance of the LSC 4.2.5 How Do Gene Alterations in the LSC Lead to the Clinical Presentation of AML? 4.3 Immunotherapy for AML 4.3.1 Antigens to Target in AML 4.3.1.1 Antigens Presented by MHC After Internal Processing 4.3.1.2 Surface Antigens 4.3.2 Current Immunotherapeutic Strategies for AML 4.3.2.1 Active Immunotherapeutic Strategies Peptide Vaccination Dendritic Cell Vaccination 4.3.2.2 Passive Immunotherapeutic Strategies Monoclonal Antibodies Adoptive T-Cell Transfer Adoptive NK Cell Transfer 4.4 Concluding Remarks References 5: Immunopathology and Immunotherapy of Acute Lymphoblastic Leukemia 5.1 Immunopathology of Lymphoblastic Leukemia 5.1.1 General Considerations 5.1.1.1 Lymphocyte Development as Biological Basis of Disease 5.1.1.2 Genetics in Acute Lymphatic Leukemia Numerical Chromosome Changes Hyperdiploid Hypodiploid Structural Changes MLL Rearrangements BCR-ABL ETV6-RUNX1 Molecular Mutations 5.1.2 Immune Phenotype and Targets in Acute Lymphatic Leukemia 5.1.2.1 Cell Surface Marker 5.1.2.2 Challenges for Immunophenotyping as MRD Marker 5.2 Immunotherapy for Acute Lymphatic Leukemia 5.2.1 Cellular Approaches 5.2.1.1 T Cells and Modified T Cells 5.2.1.2 NK Cell Approaches 5.2.2 Antibodies 5.2.2.1 CD20 Antibodies 5.2.2.2 CD22 Antibody 5.2.2.3 CD52 Antibody 5.2.2.4 CD19 Antibody Blinatumomab SGN-CD19A 5.2.3 Stem Cell Transplantation 5.2.3.1 Allogeneic Stem Cell Transplantation (Allo SCT) References 6: Immunopathology and Immunotherapy of Hodgkin Lymphoma 6.1 Introduction 6.2 Immunopathology of Hodgkin Lymphoma 6.3 General Concepts of Monoclonal Antibodies 6.3.1 The Structure of Monoclonal Antibodies 6.3.2 Choosing the Optimal Antibody 6.4 CD30 6.4.1 CD30 Monoclonal Antibodies 6.4.1.1 MDX-060 (5F11) 6.4.1.2 MDX-1401 6.4.1.3 Chimeric-AC10 6.4.1.4 SGN-30 6.4.2 CD30 mAb-Drug Conjugates 6.4.2.1 Brentuximab Vedotin 6.5 CD20 6.5.1 Rituximab 6.6 CD40 6.6.1 Lucatumumab (HCD122) 6.7 CD80 6.7.1 Galiximab (IDEC-114) 6.8 Immune Checkpoint Inhibitors 6.8.1 CTLA-4 6.8.1.1 Ipilimumab 6.8.2 PD-1 6.8.2.1 Nivolumab 6.8.2.2 Pembrolizumab 6.8.2.3 Sintilimab 6.8.2.4 Tislelizumab 6.9 Therapeutic Efficacy of Cytokines 6.9.1 Interleukin-2 (IL-2) 6.9.2 An IL-2-IL-12 Fusion Protein Targeting Hodgkin Lymphoma 6.10 Bispecific Monoclonal Antibodies 6.11 Novel Immunotherapeutic Treatment Strategies in HL 6.11.1 Immunotoxins 6.12 Chimeric Antigen Receptor-Modified T Cells 6.12.1 Anti-CD30 CAR T Cell 6.13 Concluding Remarks References 7: Immunopathology and Immunotherapy of Non-Hodgkin Lymphoma 7.1 Introduction 7.2 Immunopathology of NHL 7.3 CD30 7.3.1 M67 7.3.2 SGN-30 7.4 CD20 7.4.1 Effector Mechanisms of CD20 mAbs 7.4.2 Rituximab 7.4.2.1 Mechanisms of B-Cell Depletion by Rituximab 7.4.2.2 Rituximab in Diffuse Large B-Cell Lymphoma (DLBCL) 7.4.2.3 Rituximab in Mantle Cell Lymphoma 7.4.2.4 Rituximab in Follicular Lymphoma 7.4.2.5 Rituximab Incorporated with Carboplatin/Cisplatin-Based Chemotherapy 7.4.3 Targeting CD20 with New Anti-CD20 mAbs 7.4.4 First-Generation Anti-CD20 mAbs 7.4.4.1 Reengineered Rituximab 7.4.4.2 Tositumomab (B1) 7.4.4.3 Veltuzumab (hA20, IMMU-106) 7.4.4.4 Ocrelizumab (PRO70769, rhuH27) 7.4.5 Second-Generation CD20 mAb 7.4.5.1 Ofatumumab (Arzerra, HuMax-2F2) 7.4.6 Third-Generation CD20 mAb 7.4.6.1 PRO131921 (RhumAb v114) 7.4.6.2 AME-133v (LY2469298) 7.4.6.3 GA-101 (RO5072759, Obinutuzumab) 7.4.7 Small Modular Immunopharmaceutical Anti-CD20 Protein 7.4.7.1 TRU-015 7.5 CD22 7.5.1 Epratuzumab 7.5.2 Inotuzumab Ozogamicin (CMC-544) 7.6 CD40 7.6.1 Dacetuzumab (SGN-40) 7.6.2 Lucatumumab (HCD122, Formerly CHIR-12.12) 7.7 CD19 7.7.1 XmAb5574 7.7.2 Blinatumomab (MT102/MEDI-538) 7.7.3 hu-DM4/SAR3419 7.8 CD37 7.8.1 Tetulomab (HH1) 7.9 CD52 7.9.1 Alemtuzumab (CAMPATH-1H) 7.10 CD80 7.10.1 Galiximab (IDEC-114) 7.11 CD74 and HLA-DR 7.11.1 Milatuzumab (IMMU-115, hLL1), Naked and Conjugated 7.11.2 Apolizumab (Hu1D10, Remitogen) 7.11.3 IMMU-114 (hL243g4P) 7.11.4 LYM-1 7.11.5 Selective High-Affinity Ligands (SHALs) 7.12 CD1d and NK Cells 7.12.1 CD1d 7.12.2 Function of NK Cells in NHL 7.12.3 Adoptive Transfer of Highly Cytotoxic NK Cells 7.13 Therapeutic Efficacy of Antibody-Targeted Cytokines 7.13.1 Interferon-α (IFN-α) 7.13.2 Interleukin-2 (IL-2) 7.13.3 Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) 7.13.3.1 Mapatumumab (HGS-ETR1, TRM-1) 7.13.3.2 Lexatumumab (HGS-ETR2) 7.13.3.3 Conatumumab (AMG 655) 7.14 Novel Immunotherapeutic Treatment Strategies 7.14.1 Molecular Engineered Antibodies 7.14.2 Radioimmunoconjugates 7.14.2.1 Radioimmunotherapy for Follicular Lymphoma 7.14.2.2 CD20-Directed Radioimmunotherapy 131I-Tositumomab 90Y-Ibritumomab Tiuxetan Monotherapy 7.14.2.3 CD37-Directed RIT 7.14.3 Adoptive Cell Transfer of Genetically Modified T Cells 7.14.3.1 Redirecting T-Cell Specificity with Transgenic TCRs 7.14.3.2 Redirecting T-Cell Specificity with CARs 7.14.3.3 Other Instances of Genetic Engineering of Adoptively Transferred T Cells 7.14.4 Immune Checkpoint Blockade Therapy 7.14.5 NK Cell-Mediated Immunotherapy 7.14.6 Bispecific Antibodies 7.15 Vaccines 7.15.1 Salmonella Vaccine 7.15.2 DNA Vaccines 7.15.3 Epitope-Driven Vaccine Design 7.15.4 Preclinical Efficacy of Epitope-Driven DNA Vaccines Against B-Cell Lymphoma 7.16 Concluding Remarks References 8: Immunotherapy of Gastric and Esophageal Cancers 8.1 Introduction 8.2 Current Immunotherapeutic Modalities for Esophageal and Gastric Cancers 8.2.1 Monoclonal Antibodies 8.2.1.1 Anti-HER2 mAbs 8.2.1.2 Anti-EGFR mAbs 8.2.1.3 Anti-VEGF mAbs 8.2.1.4 Anti-MET mAbs 8.3 Adoptive Cell Therapy 8.3.1 Immune Checkpoint Inhibitors 8.3.2 Dendritic Cell-Based Vaccination in Gastric and Esophageal Cancers 8.3.3 Protein- or Peptide-Based Vaccines in Gastric and Esophageal Cancers 8.3.4 Personalized Peptide Vaccination (PPV) Immunotherapy in Gastric and Esophageal Cancer References 9: Hepatobiliary Tumors: Immunopathology and Immunotherapy 9.1 Introduction 9.2 Epidemiology 9.3 Current Treatment 9.4 Immunopathology 9.4.1 Hepatocellular Carcinoma (HCC) 9.4.2 Cholangiocarcinoma 9.4.3 Biomarker and Current Molecular Targeted Therapies 9.5 Inflammatory and Oxidative Stress Pathway 9.5.1 NF-κB Signaling Pathway 9.5.2 STAT3 Pathways 9.5.3 Cross Talk Between NF-κB and STAT3 Pathways 9.5.4 Mechanism Underlying Immunosuppression in HCC 9.6 Progress in Immunotherapy 9.6.1 Cancer Vaccines 9.6.1.1 HCC Cell Vaccines 9.6.1.2 Antigen Peptide Vaccines 9.6.1.3 DC Vaccines 9.6.2 Adoptive Cell Therapy (ACT) 9.6.3 CIK Cells 9.6.4 TILs 9.6.5 NK Cells 9.6.6 Chimeric Antigen Receptor (CAR) T Cells 9.6.7 Immune Checkpoint Inhibitors 9.6.8 CTLA-4 Inhibitors 9.6.9 PD-1 Inhibitors 9.6.10 PD-L1 Inhibitors 9.6.11 Oncolytic Viro-Therapy 9.7 Conclusion References 10: Immunology and Immunotherapy of Colorectal Cancer 10.1 Introduction: Immunity, Infection, and Inflammation 10.2 Gut Microbiota, Inflammation, and Colorectal Cancer 10.3 Obesity, Metabolic Syndrome, Cancer Cachexia, Stress, and Inflammation 10.4 CRC Prevention by Nonsteroidal Anti-inflammatory Drugs 10.5 Colorectal Cancer Microenvironment: TILs, DCs, and Tregs 10.6 Mechanisms of Immunosuppression 10.7 Immunotherapy for Colorectal Cancer 10.7.1 Consensus Molecular Subtypes of CRC 10.7.2 Key Immunotherapeutic Trials in CRC 10.7.3 Other Approaches Tested in Humans 10.7.3.1 Other Monoclonal Antibodies 10.7.3.2 Adoptive Cell Transfer 10.7.3.3 Lymphodepletion 10.7.3.4 Vaccines References 11: Immunotherapy in Nonmelanoma Skin Cancers 11.1 Introduction 11.2 Immunotherapy for Keratinocyte Cancers 11.2.1 Nonspecific Immunotherapy 11.2.1.1 Employing Delayed-Type Hypersensitivity 11.2.1.2 Interferons 11.2.1.3 Interleukin-2 11.2.1.4 Toll-Like Receptor Agonists 11.2.2 Specific Immunotherapy 11.2.2.1 Immunotherapy via Antibodies 11.2.2.2 Adoptive T-Cell Immunotherapy 11.2.2.3 Cancer Vaccines 11.2.3 Oncolytic Viruses 11.3 Conclusion References 12: Immunopathology and Immunotherapy of Melanoma 12.1 Global Statistics on Melanoma 12.2 Immunology of Melanoma 12.2.1 Inflammatory Mediators 12.2.1.1 Histopathology 12.2.1.2 Mast Cells (MCs) 12.2.1.3 Macrophages 12.2.1.4 Neutrophils 12.2.1.5 Natural Killer (NK) Cells 12.2.2 Inflammatory Pathways 12.2.2.1 Mitogen-Activated Protein Kinase (MAPK) 12.2.2.2 Nuclear Factor-kappaB (NF-κB) 12.2.3 Immune Responses 12.2.3.1 T-Cells 12.2.3.2 B-Cells 12.2.3.3 Dendritic Cells (DCs) 12.3 Immunotherapy for Melanoma 12.3.1 Immune Checkpoint Inhibitors 12.3.1.1 Efficacy 12.3.1.2 Predictive Biomarkers 12.3.1.3 Adverse Events 12.3.2 Anti-CTLA-4 Monoclonal Antibodies 12.3.2.1 Efficacy 12.3.2.2 Adverse Events Immune-Related Adverse Effects (irAEs) Death Rate Rash 12.3.3 Anti-PD-1 Monoclonal Antibodies 12.3.3.1 Efficacy 12.3.3.2 Adverse Events Vitiligo Pneumonitis Atypical Responses 12.3.4 Cytokine-Based Immunotherapies 12.3.4.1 IFN Efficacy Adverse Events 12.3.4.2 IL-2 Efficacy Adverse Events 12.3.5 Vaccines 12.3.5.1 Efficacy 12.3.5.2 Adverse Events 12.3.6 GM-CSF 12.3.7 Biochemotherapy or Chemoimmunotherapy 12.3.7.1 Efficacy 12.3.7.2 Adverse Events References 13: Immunopathology as a Basis for Immunotherapy of Head and Neck Squamous Cell Carcinoma 13.1 The Immune Profile of HNSCC 13.1.1 Immune Responses in HNSCC 13.1.2 Wt p53-Specific T-cells 13.1.3 Virus-Derived Antigen-Specific T-cells 13.1.4 Suppression of T-Cells in the Cancer-Bearing Host 13.1.5 Role of Regulatory T-Cells 13.1.6 Tumor Immune Escape 13.2 Immune Features of Tumor-Derived Exosomes 13.3 Reversing Immune Escape 13.4 Immunotherapeutic Approaches Targeting Cancer Stem Cells 13.5 Current Vaccination Strategies 13.6 Immune Checkpoint Inhibitors 13.7 Concluding Remarks References 14: Immunotherapy and Immunosurveillance of Oral Cancers: Perspectives of Plasma Medicine and Mistletoe 14.1 Introduction 14.2 Trapping an Advanced Squamous Cell Carcinoma of the Tongue by Continuous Repeated Peritumoral Injection of Mistletoe Preparation 14.3 Concluding Remarks References 15: Immunopathology of Bone and Connective Tissue Cancers and Immunotherapy of Sarcomas 15.1 Introduction 15.2 Coley’s Toxin and Toll-Like Receptors 15.3 Sarcoma Antigens as Targets for Immunotherapy 15.3.1 NY-ESO-1 15.3.2 SSX 15.3.3 ALK 15.3.4 HHV8 15.4 Preclinical Models of Immunotherapy for Sarcoma 15.4.1 Methylcholanthrene (MCA) 15.4.2 p53 and Nf1 15.5 Undifferentiated Pleomorphic Sarcoma 15.6 Clinical Applications of Immunotherapy for Sarcoma 15.6.1 Adoptive Cell Therapy 15.6.1.1 Lymphokine-Activated Killers (LAKs) 15.6.1.2 Cytokine-Induced Killers (CIKs) 15.6.1.3 Natural Killers (NKs) 15.6.1.4 Engineered T-Cells 15.6.1.5 Chimeric Antigen Receptors (CARs) 15.6.2 Sarcoma Immunotherapy of the Future: CTLA-4 and PD-1 Manipulation 15.6.2.1 CTLA-4 15.6.2.2 PD-1 15.6.2.3 Other Checkpoint Inhibitors 15.7 Concluding Remarks References 16: Immunopathology and Immunotherapy of Central Nervous System Cancer 16.1 Introduction 16.2 Antitumor Mechanisms of the Immune System 16.3 Immune Compartment of the CNS 16.4 CNS Tumor-Derived Immunosuppression 16.4.1 Tumor Cells 16.4.2 Glioma Cancer Stem Cells 16.4.3 Tumor-Associated Macrophages/Microglia 16.4.4 Myeloid-Derived Suppressor Cells 16.4.5 Lymphocytes and Regulatory T Cells 16.5 STAT3 Pathway 16.6 Cytomegalovirus in Glioma 16.7 Immunoediting in CNS Cancer 16.8 Immunotherapy 16.8.1 Adoptive Therapy 16.8.2 Vaccination Strategies 16.8.2.1 Autologous Tumor Material 16.8.2.2 Dendritic Cell-Based Vaccination Strategies 16.8.2.3 Antigen-Specific Peptide Strategies 16.8.2.4 Heat Shock Protein Peptide Complex 96 16.8.3 Immunotherapy Targeting CNS Cancer-Induced Immunosuppression 16.8.4 Monoclonal Antibodies 16.9 Concluding Remarks References 17: Immunotherapy of Lung Tumors 17.1 Introduction 17.2 Cancer Staging and Histology 17.3 The Vaccines and Cellular Therapies 17.3.1 GVAX 17.3.2 IDM-2101 17.3.3 Belagenpumatucel-L 17.3.4 MAGE-3 17.3.5 MUC1 17.3.6 EGF Vaccine 17.3.7 TG4010 17.3.8 FANG 17.3.9 Talactoferrin 17.3.10 TAG Plasmid Vaccine 17.4 Dendritic Cells 17.5 The Monoclonal Antibodies 17.5.1 Ziv-Aflibercept (Zaltrap®) 17.5.2 Bevacizumab 17.5.3 Cetuximab 17.5.4 Necitumumab 17.5.5 The EGFR Inhibitor Rash 17.5.6 Durvalumab 17.5.7 Atezolizumab 17.5.8 Pembrolizumab 17.5.9 Nivolumab 17.5.10 Ipilimumab 17.6 Adverse Effects Related to Immunotherapy 17.6.1 Measurement of Immune Response to Monoclonals 17.7 The Mutations 17.8 Chemoprevention 17.9 Discussion References 18: Immunotherapy in Bladder and Renal Cancers 18.1 Bladder cancer 18.1.1 Introduction 18.1.2 Histological Subtypes and Staging 18.1.2.1 Non-muscle Invasive Bladder Cancer 18.1.2.2 Muscle Invasive Bladder Cancer 18.1.3 Immunotherapy in Bladder Cancer 18.1.3.1 Immunotherapy in NMIBC Intravesical Bacillus Calmette–Guérin (BCG) Immunotherapy History Efficacy Side Effects Mechanism of the Antitumor Effect The Role of Bladder Cancer Cells The Role of the Immune System Optimal BCG Dose and Schedule Clinicopathologic Prognostic Factors of Non-Muscle Invasive Bladder Cancer Markers Predicting Response to BCG Cell Cycle Regulators Apoptosis Inhibitors Angiogenesis and Proliferation Markers Inflammatory Markers Cell Adhesion Molecules Combination of BCG and INF-α Checkpoint inhibitors Vaccine Therapy Gene Therapy 18.1.3.2 Immunotherapy in MIBC Checkpoint Inhibitors Atezolizumab Pembrolizumab Durvalumab Avelumab Nivolumab Ipilimumab Nivolumab and Ipilimumab Combination Pembrolizumab and Radiation Novel Tumor-Targeted Immunotherapeutics 18.2 Renal Cancer 18.2.1 Introduction 18.2.2 Immunotherapy in Renal Cancer 18.2.2.1 Localized RCC Immunotherapy Traditional Immunotherapy Vaccine-Based Therapy Antibody-Dependent Cytotoxic Agents Immune Checkpoint Inhibitors Targeted Therapy VEGF-Targeted Tyrosine Kinase Inhibitors (VEGFR-TKI) Mammalian Target of Rapamycin (mTOR) Inhibitors 18.2.2.2 Metastatic RCC Immunotherapy Historical Cytokines Vaccine-Based Therapy Adoptive T-Cell Therapy Immune Checkpoint Inhibitors Ongoing Combination Strategies Targeted Therapy VEGF Inhibitors mTOR Inhibitors 18.3 Future Directions References 19: Immunopathology of Specific Cancers in Males and Females and Immunotherapy of Prostate and Cervical Cancer 19.1 Introduction 19.2 Prostate Cancer: Past, Present, and Future 19.3 Immunotherapy of Prostate Cancer 19.4 Cervical Cancer: What We Know and What We Need to Know 19.5 The Immunotherapy of Cervical Cancer 19.6 Concluding Remarks References 20: Immunology and Immunotherapy of Ovarian Cancer 20.1 Introduction 20.2 The Role of Cytokines in Neovascularization of Epithelial Ovarian Cancer (EOC) 20.2.1 Characterization of VEGF Function 20.2.2 VEGF in Ovarian Cancer Patients 20.2.3 Role of VEGF for Ovarian Cancer Growth, Dissemination, and Metastases 20.3 The Role of Pro-Inflammatory Cytokines in Ovarian Cancer 20.3.1 Inflammation and Cancer: General Remarks 20.3.2 Inflammatory Reaction and the Risk of Ovarian Cancer 20.3.3 Inflammation and Ovarian Cancer Growth and Dissemination 20.3.3.1 Tumor Necrosis Factor-α 20.3.3.2 Interleukin-10 20.3.3.3 COX and PGE2 20.3.3.4 Interleukin-23 and Th17 Cells 20.3.3.5 Macrophage Migration Inhibitory Factor 20.3.3.6 Macrophage Colony-Stimulating Factor 20.3.3.7 Chemokines 20.4 Regulatory and Inflammatory Cells in Ovarian Cancer 20.5 Immune Checkpoint Proteins and Their Inhibitors 20.5.1 The CTLA-4 Checkpoint Molecule 20.5.2 The PD-1 Checkpoint Molecule 20.5.2.1 Anti-PD-1/PD-L1 Monoclonal Antibodies in Animal and Human Trials 20.6 Cytokines in Diagnosis and Prognosis of Ovarian Cancer 20.6.1 Diagnosis 20.6.2 Prognosis 20.7 Immunotherapy of Ovarian Cancer 20.7.1 Monoclonal Antibodies 20.7.1.1 Bevacizumab 20.7.1.2 Catumaxomab 20.7.1.3 Oregovomab and Abagovomab 20.7.1.4 Trastuzumab and Pertuzumab 20.7.1.5 Farletuzumab 20.7.2 Cytokines 20.7.3 Cancer Vaccines 20.7.3.1 Dendritic Cell-Based Vaccines 20.7.3.2 Peptide-Based, Genetic and Epigenetic Vaccines 20.7.4 Adoptive Immunotherapy Using Autologous T-Cells 20.7.5 Cytokine-Induced Killer Cells 20.7.6 Chimeric Antigen-Receptor T-Cells (CAR-T Cells) 20.7.7 Targeting Tumor-Associated Macrophages (TAMs) 20.8 Conclusion References 21: Immunopathology and Immunotherapy for Breast Cancer 21.1 Introduction 21.2 Breast Cancer and the Immune System 21.3 Gene Expression and Molecular Classification 21.4 Immunotherapy for Breast Cancer 21.4.1 Targeted Therapy by Using Monoclonal Antibodies (mAb) 21.4.2 Vaccines 21.4.3 Immune Checkpoint Inhibitors 21.4.3.1 Anti-CTLA-4 Antibodies 21.4.3.2 Anti-PD-1 Antibodies 21.4.3.3 Anti-PD-L1 Antibodies 21.4.4 Adoptive T-cell therapy 21.5 Conclusion References 22: Immunology and Immunotherapy of Graft-Versus-Host Disease 22.1 Introduction 22.2 GVHD 22.3 Pathogenesis of Acute GVHD 22.3.1 Phase I: Conditioning 22.3.2 Phase II: Activation 22.3.3 Phase III: Effector Phase 22.4 Natural Control of GVHD 22.5 Graft-Versus-Tumor Effect 22.6 Prevention of GVHD 22.7 Treatment of Acute GVHD 22.8 Targeted Approaches 22.8.1 Targeting Cytokines 22.8.2 Targeting Co-stimulation 22.8.3 Targeting Cell Subsets 22.8.3.1 B Cells 22.8.3.2 NK Cells 22.8.3.3 Mesenchymal Stem Cells 22.8.3.4 Treg Cells 22.9 Concluding Remarks References Index