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

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
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