Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

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Part 2 Immune Evasion and Suppression 57 5 Major Histocompatibility Complex Modulation and Loss 59 Barbara Seliger and Ulrike Ritz 5.1 The Major Histocompatibility Complex (MHC) Antigen-Processing and -Presentation Pathways 59 5.1.1 The MHC Class I Antigen-Processing Machinery (APM) 60 5.1.2 The MHC Class II APM 61 5.2 The Physiology of the Non-classical HLA-G Molecule 63 5.3 Determination of the Expression of Classical and Non-classical MHC Antigens 63 5.4 Interaction between Tumor and the Immune System 65 5.5 The Different MHC Class I Phenotypes and their Underlying Molecular Mechanisms 66 5.5.1 MHC Class I Loss 67 5.5.2 MHC Class I Down-regulation 69 5.5.3 Selective Loss or Down-regulation 72 5.6 MHC Class I Alterations: Impact on Immune Responses and Clinical Relevance 76 5.7 The Role of MHC Class II Processing and Presentation in Tumors 79 5.7.1 Frequency and Clinical Impact of MHC Class II Expression on Tumors 79 5.7.2 Molecular Mechanisms of Deficiencies in the MHC class II APM 81 5.7.3 Modulation of Immune Response by Altered MHC Class II Expression 81 5.7.4 MHC Class II Expression in Antitumor Response 82 5.8 Role of IFN-c in Immunosurveillance 83 5.8.1 IFN-c-dependent Immunosurveillance of Tumor Growth 84 5.8.2 Deficiencies in the IFN Signal Transduction Pathway 85 5.9 HLA-G Expression: an Immune Privilege for Malignant Cells? 85 5.9.1 HLA-G Expression in Tumor Cells of Distinct Origin 86 5.9.2 Clinical Impact of HLA-G Expression 88 5.9.3 Induction of Tolerance by HLA-G Expression 88 5.10 Conclusions 88 Acknowledgments 89 References 89 6 Immune Cells in the Tumor Microenvironment 95 Theresa L. Whiteside 6.1 Introduction 95 6.2 The Immune System and Tumor Progression 95 6.3 Immune Cells in the Tumor Microenvironment 97 6.4 Phenotypic and Functional Characteristics of Immune Cells Present at the Tumor Site 99 6.4.1 T Cells 99 Contents IX
X Contents 6.4.2 Natural Killer (NK) Cells 101 6.4.3. DCs 105 6.4.4 Macrophages 107 6.4.5 B Cells 108 6.5 Mechanisms Linked to Dysfunction of Immune Cells in Cancer 108 6.5.1 The CD95±CD95 Ligand (CD95L) Pathway 110 6.5.2 T Lymphocyte Apoptosis in Patients with Cancer 111 6.5.3 Tumor Sensitivity to FasL-Mediated Signals 111 6.5.4 A Dual Biologic Role of FasL 112 6.5.5 Contributions of other Pathways to Lymphocyte Demise in Cancer 112 6.6 Conclusions 113 References 115 7 Immunosuppressive Factors in Cancer 119 Richard Bucala and Christine N. Metz 7.1 Introduction 119 7.1 Transforming Growth Factor (TGF)-b 119 7.1.1 Sources of TGF-b 121 7.1.2 Effects of TGF-b 121 7.1.2.1 Effects of TGF-b on monocytes/macrophages 121 7.1.2.2 Effects of TGF-b on T lymphocytes 122 7.1.2.3 Effects of TGF-b on NK and lymphokine-activated killer (LAK) activity 123 7.1.2.4 Effects of TGF-1;b on dendritic cells (DCs) 123 7.1.3 Inhibition of TGF-b: Implications for Therapy 124 7.2 IL-10 125 7.2.1 Sources of IL-10 125 7.2.2 Effects of IL-10 126 7.2.2.1 Effects of IL-10 on monocytes/macrophages 126 7.2.2.2 Effects of IL-10 on T lymphocytes 126 7.2.2.3 Effects of IL-10 on NK cells 128 7.2.2.4 Effects of IL-10 on DCs 128 7.2.3 Inhibition of IL-10: Implications for Therapy 128 7.2.3.1 Antibodies 129 7.2.3.2 Drugs 129 7.2.3.3 Removal of the source of IL-10 129 7.3 Macrophage Migration Inhibitory Factor (MIF) 130 7.4 Prostaglandin (PG) E2 131 7.4.1 Sources of PGE2 131 7.4.2 Effects of PGE2 131 7.4.2.1 Effects of PGE 2 on monocytes/macrophages 131 7.4.2.2 Effects of PGE2 on T lymphocytes 131 7.4.2.3 Effects of PGE2 on NK cells and LAK activity 132 7.4.3 Inhibition of PGE2: Implications for Therapy 132 7.5 Polyamines 132
Page 1 and 2: Cancer Immune Therapie: Current and
Page 3 and 4: Editors: Dr. Gernot Stuhler Univers
Page 5 and 6: VI Preface Recent years have seen a
Page 7: VIII Contents 2.5.3 Antigens Encode
Page 11 and 12: XII Contents 9.6 Loading DC with An
Page 13 and 14: XIV Contents 14.2.2.1 Cancer-specif
Page 15 and 16: List of Contributors Richard Bucala
Page 17 and 18: Color Plates Fig. 5.2 The MHC class
Page 19 and 20: Fig. 5.5 Different immune effector
Page 21 and 22: Fig. 5.17 Possible pathway for the
Page 23 and 24: Fig. 6.2 T lymphocytes in the tumor
Page 25 and 26: Index a acidic and basic fibroblast
Page 27 and 28: ±, see also tumors cationic lipids
Page 29 and 30: e EBV see Epstein-Barr virus EDR se
Page 31 and 32: immature Mo-DCs 184 immune cells ±
Page 33 and 34: MHC class I antigen-processing mach
Page 35 and 36: ±, onco- 209 ±, over-expressed ce
Page 37 and 38: TICD see tumor-induced cell death T
Page 39 and 40: Part 1 Tumor Antigenicity Cancer Im
Page 41 and 42: 4 1 Search for Universal Tumor-Asso
Page 47 and 48: 10 1 Search for Universal Tumor-Ass
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22 2 Serological Determinants On Tu
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30 Cancer Immune Therapie: Current
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32 3 Processing and Presentation of
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42 4 T Cells In Tumor Immunity cult
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44 4 T Cells In Tumor Immunity cell
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46 4 T Cells In Tumor Immunity to T
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48 4 T Cells In Tumor Immunity Alth
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50 4 T Cells In Tumor Immunity Tab.
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52 4 T Cells In Tumor Immunity rest
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54 4 T Cells In Tumor Immunity 53 T
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Part 2 Immune Evasion and Suppressi
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60 5 Major Histocompatibility Compl
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68 Tab. 5.1 HLA class I loss attrib
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96 6 Immune Cells in the Tumor Micr
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100 6 Immune Cells in the Tumor Mic
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Tab. 7.1 Effects of tumor-derived m
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122 7 Immunosuppresive Factors in C
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156 8 Interleukin-10 in Cancer Immu
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Part 3 Strategies for Cancer Immuno
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180 9 Dendritic Cells and Cancer: P
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206 10 The Immune System in Cancer:
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232 11 Hybrid Cell Vaccination for
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254 12 Principles and Strategies Em
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270 13 Applications of CpG Motifs f
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288 14 The T-Body Approach: Towards
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300 15 Bone Marrow Transplantation
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312 16 Immunocytokines: Versatile M
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348 17 Immunotoxins and Recombinant
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382 Glossary tion to the variable d
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384 Glossary suppressor gene produc
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386 Glossary press the proper recep
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388 Glossary gp96 See Chaperone. Gr
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390 Glossary cytes and addressing l
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392 Glossary T bodies are being tes
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