CANCER IMMUNOLOGY cancer immunotherapy for organ specific tumors.

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