Interaction of immune and cancer cells

Preface
Contents
List of Contributors
Chapter 1: Cancer Immunoediting: Elimination, Equilibrium, and Immune Escape in Solid Tumors
	1.1 Introduction
	1.2 Immunosurveillance of the Host Against Cancer-Elimination
	1.3 Cancer Dormancy and Cancer-Immune Equilibrium
	1.4 Cancer Escape Mechanisms
		1.4.1 Disruption of the Antigen-Presenting Machinery, HLA-G, and Costimulatory Molecules
		1.4.2 Tumor-Infiltrating Lymphocytes and Immune Escape
		1.4.3 Immunoregulatory Function of Tumor-Associated Myeloid Cells (TAMCs)
		1.4.4 Dendritic Cells as Tumor Growth Enhancers
		1.4.5 Inflammation and Cancer Escape
		1.4.6 Resistance to Apoptosis and Tumor ``Counter Attack´´
		1.4.7 The Role of Tumor Stroma in Immune Escape
		1.4.8 Microvesicles and Exosomes-Mediators of Tumor Escape
	1.5 Conclusions
	References
Chapter 2: Tumor: Stroma Interaction and Cancer
	2.1 Introduction
	2.2 TME: The Nonimmune Components
		2.2.1 Epithelial Cells
		2.2.2 Basement Membrane and Extracellular Matrix
	2.3 TME: The Immune Components, Chronic Inflammation, Wound Healing, and Tumor Progression
	2.4 EMT and TGF-β
		2.4.1 TGF-β Signaling
	2.5 Osteopontin and EMT
	2.6 Summary
	References
Chapter 3: Tumor-Infiltrating Lymphocytes and Their Role in Solid Tumor Progression
	3.1 Introduction
	3.2 Studies of the Intratumor Immune Landscape
	3.3 Immune Score in the TME
	3.4 Antitumor Effects of TIL
		3.4.1 CD8+ Cytolytic T Cells
		3.4.2 CD4+ Helper T Cells
		3.4.3 Regulatory T Cells (Treg)
		3.4.4 B Cells
		3.4.5 Natural Killer (NK) Cells
	3.5 Summary and Conclusions
	References
Chapter 4: Tumor-Associated Macrophages: Reasons to Be Cheerful, Reasons to Be Fearful
	4.1 Introduction
	4.2 Classification of Macrophages
	4.3 Characterization of Tumor-Associated Macrophages
	4.4 Role of TAMs in Cancer Initiation, Promotion, and Progression
		4.4.1 TAMs in Chronic Inflammation
		4.4.2 TAMs in Metastasis and Premetastatic Niche
		4.4.3 TAMs in Angiogenesis
		4.4.4 TAMs in Antitumor Immune Response Suppression
	4.5 TAMs in Cancer Therapy
	4.6 Therapeutic Approaches of Targeting TAMs-From Experimentation to Clinical Trials
	4.7 Conclusions
	References
Chapter 5: Polymorphonuclear Neutrophils and Tumors: Friend or Foe?
	5.1 Introduction
	5.2 Characterization of Tumor-Associated Neutrophils
		5.2.1 Requirement of Neutrophils to the Tumor Tissue
		5.2.2 Heterogeneity of Tumor-Associated Neutrophils
	5.3 Dual Role of TANs in TME
	5.4 Antitumoral Effect of TANs
		5.4.1 ROS Production
		5.4.2 Fas/FasL System
		5.4.3 Trail
		5.4.4 Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)
	5.5 Protumoral Effects of TANs
		5.5.1 Neutrophil Elastase (NE)
		5.5.2 Matrix Metalloproteinase-9 (MMP-9)
		5.5.3 Oncostatin M (OSM)
		5.5.4 Cathepsin G (CG)
		5.5.5 Arginase 1 (ARG-1)
		5.5.6 PD-L1
		5.5.7 Neutrophils Extracellular Traps (NETs)
		5.5.8 Tumor Cell Extravasation
	5.6 Conclusion
	References
Chapter 6: Role of NK Cells in Tumor Progression
	6.1 Introduction
	6.2 NK Cell Biology
		6.2.1 NK Cell Diversity
		6.2.2 NK Cell Effector Functions
	6.3 Mechanisms of Tumor Resistance to NK Cell-Mediated Killing
	6.4 NK Cells in Tumor Progression
		6.4.1 NK Cell Infiltration in the TME
		6.4.2 Phenotype of TINK Cells
		6.4.3 Prognostic Value of NK Cells
	6.5 Concluding Remarks
	References
Chapter 7: The Role of Myeloid-Derived Suppressor Cells in Tumor Growth and Metastasis
	7.1 Introduction
		7.1.1 MDSC Subsets
		7.1.2 Lineage Relationship of MDSCs
		7.1.3 MDSCs in Cancer
	7.2 Signaling Networks Driving MDSCs in Cancer
		7.2.1 Recruitment
		7.2.2 Maintenance and Function
	7.3 Differential Roles of MDSC Subsets in Cancer
	7.4 Conclusion
	References
Chapter 8: Cancer Stem Cells: An Ever-Hiding Foe
	8.1 Introduction: Cancer Stem Cells: Definition and General Description
	8.2 Cancer Stem Cells Markers
	8.3 Cancer Stem Cells Signaling Pathways
	8.4 Genetic and Epigenetic Regulation of Cancer Stem Cells
	8.5 Cancer Stem Cells and EMT Transition
	8.6 Cancer Stem Cells and Tumor Microenvironment Niche
	8.7 Cancer Stem Cells and Autophagy
	8.8 Cancer Stem Cells and Immunosurveillance
	8.9 Conclusion
	References
Chapter 9: Adoptive T-cell Immunotherapy: Perfecting Self-Defenses
	9.1 Introduction
	9.2 Tumor Antigens and Microenvironment: Opportunities and Hurdles
		9.2.1 Tumor Antigens: The Target of the Immune System
		9.2.2 Tumor Microenvironment (TME): Halting the Immune Response
		9.2.3 Inhibitory Cytokines: Another Major Hurdle in the TME
		9.2.4 Cancer Metabolism: The Object of a Renewed Interest
		9.2.5 Inhibitory Receptors and Immune Checkpoints Inhibitors
	9.3 T-cell lymphocyte-Based Immunotherapy
		9.3.1 Tumor-Infiltrating-Lymphocytes (TILs)
			9.3.1.1 TIL Treatment
			9.3.1.2 TIL Therapy Implications and Future Promises
		9.3.2 Genetic Engineering of T-Cells
			9.3.2.1 TCR Structure: A Critical Determinant of T-Cell Function
			9.3.2.2 TCR-Gene Transfer
		9.3.3 Limits of TCR Gene Transfer and Ways to Address Them
	9.4 CAR-T-Cells
		9.4.1 CAR-T-Cell Therapy: Structure and Development
		9.4.2 Driving the CARs to the Clinic
		9.4.3 CAR Limits
		9.4.4 CAR-T-Cells Variations
	9.5 Additional Strategies for T-Cell Engineering
		9.5.1 Editing Platforms in Gene Engineering
		9.5.2 Beyond TCR and CAR Engineering
	9.6 Conclusions
	References
Chapter 10: Monoclonal Antibodies to CTLA-4 with Focus on Ipilimumab
	10.1 CTLA-4
	10.2 CTLA-4 as Pharmacological Target for Immunosuppression or Immunostimulation
	10.3 Ipilimumab
		10.3.1 Clinical Efficacy Studies with Ipilimumab
			10.3.1.1 Malignant Melanoma
				Clinical Studies with Ipilimumab as Monotherapy
				Clinical Studies with Ipilimumab in Combination with Nivolumab
			10.3.1.2 Renal Cell Carcinoma
			10.3.1.3 Colorectal Cancer
			10.3.1.4 NSCLC
			10.3.1.5 Hepatocellular Carcinoma
			10.3.1.6 Malignant Pleural Mesothelioma
			10.3.1.7 Phase III Clinical Trials in Prostate Cancer and Other Solid Tumours
	10.4 Criteria to Evaluate the Efficacy of Immune-Checkpoint Inhibitors
	10.5 Adverse Effects
		10.5.1 Skin Toxicity
		10.5.2 Colitis and Diarrhoea
		10.5.3 Hepatitis
		10.5.4 Endocrinopathies
		10.5.5 Other irAEs
	10.6 Conclusions
	References