Yefenof Innate and Adaptive Immunity in the Tumor Microenvironment

1. Auflage 2007
ISBN: 978-1-4020-6750-1
Verlag: Springer-Verlag
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 212 Seiten

Cancer cells are continuously interacting with the immune system of the host. These interactions can be regarded as a double edged sword. On the one hand, innate and adaptive immune responses act to protect the host by attempting rejection of the tumor. On the other hand, inflammatory cells and proteins stimulate multiplication and dissemination of cancer cells, thereby accelerating the progression of the disease. Traditionally, the interplay between cancer cells and host immunity has been studied systemically, with no particular attention to the site at which a given tumor develops. Recent studies, however, indicate that the tumor microenvironment is unique in providing both supportive and inhibitory factors that determine the fate of the tumor and its host. Accordingly, microenvironmental immunity that operates inside and around a tumor plays a crucial role in cancer development and progression. The aim of the present volume is to compile reviews on innate and adaptive immune responses at the tumor microenvironment with emphasis on positive and negative outcomes that affect the progression of the disease. These reviews have been solicited from experts in the field who published original research studies focusing on these issues.

Autoren/Hrsg.

Yefenof, Eitan

Inhaltsverzeichnis

1;Foreword;5
1.1;Tumor Microenvironment under the Magnifying Glass: A New Challenge to Cancer Immunologists;5
2;Contents;9
3;List of Contributors;11
4;Immune Effector Cells in the Tumor Microenvironment;13
4.1;1.1 Introduction;13
4.2;1.2 Evidence for Loco-regional Immune Dysfunction in Cancer;15
4.2.1;1.2.1 Biologic Significance of Loco-regional Immune Suppression;16
4.3;1.3 Evidence for Systemic Immune Deviation in Cancer;17
4.4;1.4 Mechanisms Responsible for Dysfunction of Immune Cells in Cancer Patients;17
4.4.1;1.4.1 Interference with the Induction of TAA-specific Responses;18
4.4.2;1.4.2 Interference with Functions/Survival of Effector T Lymphocytes;23
4.4.3;1.4.3 A loss of Tumor Recognition by Immune Cells;28
4.4.4;1.4.4 Resistance of Tumor Cells to Immune Intervention;31
4.4.5;1.4.5 Tumor-derived Suppressive Factors;33
4.5;1.5 Conclusions;33
4.6;References;34
5;Histocompatibility Antigens, Tumor Microenvironment and Escape Mechanisms Utilized by Tumor Cells;46
5.1;2.1 Introduction;46
5.2;2.2 Classical and Non-Classical HLA Class I Antigens and NK- Cell Activating Ligands in Malignant Lesions;47
5.3;2.3 Antigen Presentation by HLA Class I Antigens;50
5.4;2.4 Modulation of APM Components by Cytokines in the Tumor Microenvironment;52
5.4.1;2.4.1 IL-10;53
5.4.2;2.4.2 Transforming Growth Factor-b (TGF-b);54
5.4.3;2.4.3 Interferon-g (IFN-g );55
5.5;2.5 Potential Effects of Released Classical and Non-Classical HLA Class I Antigens and NK- Cell Activating Ligands in the Tumor Microenvironment;56
5.6;2.6 Conclusions;57
5.7;References;59
6;Local Tumor Growth and Spontaneous Systemic T Cell Responses in Cancer Patients: A Paradox and Puzzle;63
6.1;3.1 Introduction;63
6.2;3.2 Spontaneous T Cell Immunity and the Tumor Microenvironment;64
6.2.1;3.2.1 Spontaneous Systemic T Cell Responses in Cancer Patients;64
6.2.2;3.2.2 The Bone Marrow as a Source of Tumor-reactive T Cells;66
6.2.3;3.2.3 Systemic T Cell Immunity and T Cell Entry into Tumor Tissue;69
6.2.4;3.2.4 The Tumor Microenvironment and the Induction and Function of Tumor Specific T Cells;71
6.3;3.3 Intervention in Tumor Microenvironment ;75
6.3.1;3.3.1 Counteracting Immune Deregulation;75
6.3.2;3.3.2 Counteracting Metabolic Deregulation;78
6.3.3;3.3.3 Intervention by Physical Means: Radiation, Hyperthermia, Electrochemical Therapy;78
6.3.4;3.3.4 Intra-Tumoral Delivery of Viral Vectors or Slow- release Systems;79
6.3.5;3.3.5 Locoregional Interference Via Port Systems;80
6.4;3.4 Future Directions;80
6.5;References;81
7;Insights into Mechanisms of Immune Resistance in the Tumor Microenvironment through Molecular Profiling;87
7.1;4.1 Introduction;87
7.2;4.2 Melanoma Microenvironment Analysis Through Gene Expression Profiling;88
7.3;4.3 Regulation of Migration into Tumor Metastases;89
7.4;4.4 Inhibitory Mechanisms in the Tumor Microenvironment;91
7.5;4.5 Resistance at the Level of the Tumor Cells Themselves;94
7.6;4.6 Relevance of Understanding the Melanoma Microenvironment to Immunotherapy Clinical Trials;94
7.7;References;96
8;Tumor Antigens as Modulators of the Tumor Microenvironment;100
8.1;5.1 Introduction;100
8.2;5.2 Mr. Hyde MUC1 Promotes Tumorigenesis;102
8.3;5.3 Dr. Jekyll MUC1 is a Tumor Antigen Targeted by Immune Surveillance;103
8.4;5.4 Mr. Hyde MUC1 Manipulates Tumor Microenvironment;105
8.5;5.5 Other Dr. Jekyll and Mr. Hyde-Like Tumor Antigens ;106
8.5.1;5.5.1 Dr. Jekyll CEA;106
8.5.2;5.5.2 Mr. Hyde CEA;108
8.5.3;5.5.3 Dr. Jekyll Tumor Glycolipids;108
8.5.4;5.5.4 Mr. Hyde Tumor Glycolipids;109
8.5.5;5.5.5 Dr. Jekyll gp100;110
8.5.6;5.5.6 Mr. Hyde gp100;110
8.6;5.6 Cancer Stem Cells and their Dr. Jekyll and Mr. Hyde Antigens;111
8.7;5.7 Candidate Cancer Stem Cell Markers;112
8.8;5.8 The Stem Cell Niche as the Tumor Microenvironment;114
8.9;5.9 Signaling Pathways that Control Cancer Stem Cell Function;115
8.10;5.10 Cancer Stem Cell Antigens and the Tumor Microenvironment;115
8.11;5.11 Targeting Tumor Antigens to Change Tumor Microenvironment and Restore Immunosurveillance;117
8.12;Abbreviations;118
8.13;References;118
9;Tumor Cell Resistance to Apoptosis by Infiltrating Cytotoxic Lymphocytes;129
9.1;6.1 Introduction;130
9.2;6.2 Apoptosis as a Cytotoxic Mechanism Induced by Cytotoxic Lymphocytes;131
9.3;6.3 Inhibition of Apoptosis as a Mechanism of Cross Resistance;132
9.4;6.4 Mechanisms of Resistance to Cytotoxic Immune Cells ;132
9.4.1;6.4.1 Extrinsic;132
9.4.2;6.4.2 Intrinsic;133
9.5;6.5 Sensitization of Resistant Tumor Cells to Cytotoxic Lymphocytes/ Factors- mediated Apoptosis;134
9.5.1;6.5.1 Chemosensitizing Drugs as Immunosensitizing Agents;134
9.5.2;6.5.2 Nitric Oxide (NO) Donors as Immunosensitizing Agents;136
9.5.3;6.5.3 Antibody-mediated Immunosensitization;137
9.5.4;6.5.4 Pharmacologic Inhibitors;137
9.6;6.6 Influence of the Tumor Microenvironment on the Development of Tumor Cell Resistance to Cytotoxic Therapy;138
9.7;6.7 Therapeutic Implications;139
9.8;6.8 Concluding Remarks;139
9.9;References;140
10;The Tumor Microenvironment as a Model for Tissue- Specific Rejection;146
10.1;7.1 Introduction;146
10.1.1;7.1.1 Innate Immunity and Inflammation;150
10.1.2;7.1.2 Dendritic Cells;150
10.1.3;7.1.3 NK Cells;151
10.1.4;7.1.4 T Cells;152
10.1.5;7.1.5 Tumor Cells;155
10.2;References;156
11;Functional Cytotoxicity of T Cells in the Tumor Microenvironment;163
11.1;8.1 Introduction;163
11.2;8.2 Early Events: Antigen Presentation, CTL Activation and Migration;164
11.3;8.3 The Immune Synapse;165
11.4;8.4 Functional CTL Capture Membrane Fragments from Tumors;166
11.5;8.5 Killing Mechanisms of CTLs;169
11.5.1;8.5.1 Cytotoxins;169
11.5.2;8.5.2 Cytokines;170
11.5.3;8.5.3 Membrane-associated Proteins;170
11.6;8.6 Future Research Directions to Improve Functional Cytotoxicity of Tumor- specific CTLs;171
11.7;References;172
12;Natural Killer Cells at the Tumors Microenvironment;177
12.1;9.1 Introduction;177
12.2;9.2 Basic Properties of Natural Killers;177
12.3;9.3 The Presence of NK Cells Inside Tumors;178
12.4;9.4 Trafficking to the Tumor Site;179
12.5;9.5 Innate Recognition of Tumor Cells;180
12.6;9.6 Modulation of Tumor Recognition by NK Cells;181
12.7;9.7 MHC Class-I Independent Inhibition of NK Cells;183
12.8;9.8 Effector Functions and Tumor Development;183
12.9;9.9 TNF Family Ligands;184
12.10;9.10 The Influence of Physico-chemical Microenvironment on NK Cells;185
12.11;9.11 IL-10;186
12.12;9.12 TGF-ß;186
12.13;9.13 NK–DCs Interactions;187
12.14;9.14 Suppression of NK by Immune-regulatory Cells;188
12.15;9.15 Killing of Metastatic Cancerous Cells by NK;189
12.16;9.16 Concluding Remarks;189
12.17;References;189
13;Contribution of the Microenvironment to the Pathogenesis of EBV- Positive Hodgkin and Nasal NK/ T- cell Lymphomas;200
13.1;10.1 Background;200
13.2;10.2 Expression of EBV-encoded Proteins in Lymphocytes with Latent Infection;202
13.3;10.3 The Changes of Viral Expression Concomitant with B- cell Maturation;203
13.4;10.4 EBV-carrying Hematopoetic Malignancies with Type IIa Restricted Viral Gene Expression;204
13.4.1;10.4.1 Hodgkin lymphoma, HL;205
13.4.2;10.4.2 Extranodal, Nasal NK/T-cell Lymphoma;208
13.5;10.5 Conclusion;210
13.6;References;211
14;Index;215