Tumor Microenvironment: Hematopoietic Cells – Part A (Advances in Experimental Medicine and Biology, 1224)

Preface
Contents
Contributors
1: Neutrophils in the Tumor Microenvironment
	1.1	 Introduction
	1.2	 Neutrophil Life Cycle
		1.2.1	 Granulopoiesis
		1.2.2	 Neutrophil Dynamics: From Bone Marrow to the Circulation
	1.3	 Neutrophil Population in Health and Disease
		1.3.1	 Neutrophil Frequency and Phenotype in Cancer
		1.3.2	 Low-Density Neutrophils (LDNs)
		1.3.3	 Myeloid-Derived Suppressor Cells (MDSCs)
		1.3.4	 Tumor-Associated Neutrophils (TANs)
	1.4	 Functions of Neutrophils in the Tumor Microenvironment
		1.4.1	 Neutrophil-Released Reactive Oxygen Species (ROS)/Reactive Nitrogen Species (RNS)
		1.4.2	 Neutrophil-Secreted Cytokines and Chemokines
		1.4.3	 Neutrophil-Released Enzymes
		1.4.4	 Neutrophil Extracellular Traps (NETs)
	1.5	 Role of Neutrophil in Tumor Initiation, Growth, and Metastasis
		1.5.1	 The Role of Neutrophils in the Early Metastatic Cascade
		1.5.2	 Role of Neutrophils in Intermediate Metastatic Cascade
		1.5.3	 Role of Neutrophils in the Late Metastatic Cascade
	1.6	 The Clinical Significance of Neutrophils
		1.6.1	 Neutrophils as a Potential Biomarker for Cancer Patients
		1.6.2	 Neutrophils as Therapeutic Targets in Cancer Patients
	1.7	 Concluding Remarks
	References
2: Basophils in Tumor Microenvironment and Surroundings
	2.1	 General Aspects
	2.2	 Basophils as a Source of Cytokines, Chemokines, Angiogenic Molecules, and Granzyme B
	2.3	 Are Mouse and Human Basophils Antigen-Presenting Cells (APCs)?
	2.4	 Basophil-Deficient Mice
	2.5	 Peripheral Blood Basophils and Human Cancer
	2.6	 Basophils in Tumor Microenvironment of Human Lung Adenocarcinoma
	2.7	 Basophils in Experimental Melanoma
	2.8	 Basophils in Experimental and Human Pancreatic Cancer
	2.9	 Conclusions and Outstanding Questions
	References
3: Janus or Hydra: The Many Faces of T Helper Cells in the Human Tumour Microenvironment
	3.1	 Introduction
	3.2	 Dual Role of T Helper Cells in Tumour Development and Progression
		3.2.1	 T Helper Type 1
		3.2.2	 T Helper Type 2
		3.2.3	 Regulatory T Cells
		3.2.4	 T Helper Type 17
		3.2.5	 T Follicular Helper
		3.2.6	 T Helper Type 9
		3.2.7	 T Helper Type 22
	3.3	 Regulation of T Helper Cell Homing and Differentiation in the TIME
		3.3.1	 Homing of Regulatory T Cells
		3.3.2	 Dendritic Cells as Key Regulators of TIME Composition
	3.4	 T Helper Cells in the Context of Immunotherapy
	3.5	 Prognostic Role of T Helper Cells
	3.6	 Conclusions
	References
4: Cytotoxic CD8+ Lymphocytes in the Tumor Microenvironment
	4.1	 Introduction
	4.2	 CD8+ T Cells in the Tumor Microenvironment
	4.3	 Tumor Antigen-Specific T Cells for Cancer Immunotherapy
	4.4	 Detection of Cytotoxic T Cells in the Tumor Microenvironment
	4.5	 Relationship Between Cytotoxic T Cells in Tumors and Peripheral Blood
	4.6	 Future Directions
	References
5: Mucosal-Associated Invariant T Cells in Tumors of Epithelial Origin
	5.1	 Introduction
	5.2	 Microbes and Cancer
		5.2.1	 Colorectal Cancer
		5.2.2	 Gastric Cancer
		5.2.3	 Breast Cancer
		5.2.4	 Hepatocellular Carcinoma
	5.3	 MAIT Cells and Microbes
		5.3.1	 Activation Pathways
		5.3.2	 Role of Inflammation
		5.3.3	 Differing Antigenicity of Bacterial Species
	5.4	 MAIT Cells and Cancer
		5.4.1	 Colorectal Cancer (CRC)
		5.4.2	 Hepatocellular Carcinoma (HCC)
		5.4.3	 Gastric Cancer
		5.4.4	 Cervical Cancer
		5.4.5	 Breast Cancer
	5.5	 Conclusion
	References
6: Fibrocytes in the Tumor Microenvironment
	6.1	 Introduction
	6.2	 Fibrocytes in Benign Tumors
	6.3	 Fibrocytes in Malignant Tumors
	6.4	 Fibrocytes in Metastasis
	6.5	 Conclusion and Future Directions
	References
7: Models for Monocytic Cells in the Tumor Microenvironment
	7.1	 Introduction
		7.1.1	 Monocyte Ontogeny
		7.1.2	 Monocyte Heterogeneity
	7.2	 Monocyte Functions in Cancer
		7.2.1	 Recruitment to Tumors
		7.2.2	 Tumoricidal Activity
		7.2.3	 Differentiation into TAMs and moDCs
		7.2.4	 Interaction with Tumor Microenvironment (TME) Matrix
		7.2.5	 Pro-angiogenic Effects
		7.2.6	 Establishing the Pre-metastatic Niche
		7.2.7	 Interaction with T Cells
	7.3	 Therapeutic Applications Related to Cells of Monocytic Origin
		7.3.1	 Biomarkers for Prognosis
		7.3.2	 Combinational Therapeutic Strategies
			7.3.2.1	 Monocyte-Associated Strategies
			7.3.2.2	 TAM- or moDC-Associated Strategies
		7.3.3	 Autologous Monocytic Cell Therapy
		7.3.4	 Nano-immunotherapy
	7.4	 Experimental Cancer Models for Studying Monocytes
		7.4.1	 Conventional 2D In Vitro Cancer Models
		7.4.2	 Conventional 3D Cancer Models
		7.4.3	 Comparative Studies of 2D Versus 3D In Vitro Cancer Models
		7.4.4	 Microfluidic Cancer Models
			7.4.4.1	 Microfluidic Cancer Models to Study Monocytes
			7.4.4.2	 Microfluidic Cancer Models to Study Monocyte-Derived Cells
			7.4.4.3	 Patient-Derived Microfluidic Cancer Models
	7.5	 Future Directions
	References
8: Myeloid-Derived Suppressor Cells in the Tumor Microenvironment
	8.1	 Introduction
	8.2	 Defining Human and Murine MDSCs
		8.2.1	 Defining MDSCs in the Periphery
		8.2.2	 Defining MDSCs Within Tumors
	8.3	 MDSC Development and Expansion
		8.3.1	 Signal 1
		8.3.2	 Signal 2
	8.4	 Mechanisms of MDSC Suppression
	8.5	 Non-immunologic Functions of MDSCs
	8.6	 Clinical Significance of MDSCs
	8.7	 Therapeutic Targeting of MDSCs
		8.7.1	 Inhibiting MDSC Expansion and Trafficking
		8.7.2	 Differentiating MDSCs into Mature Cells
		8.7.3	 Inhibiting MDSC Suppressive Function
		8.7.4	 Depleting MDSCs from the TME
	8.8	 MDSCs in Non-oncologic Conditions
	8.9	 Trends and Future Directions
	References
Index