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

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VIII Contents<br />

2.5.3 Antigens Encoded <strong>by</strong> Mutated Genes 21<br />

2.5.4 Viral Genes 22<br />

2.5.5 Antigens Encoded <strong>by</strong> Over-expressed Genes 22<br />

2.5.6 Amplified Genes 22<br />

2.5.7 Splice Variants of Known Genes 22<br />

2.5.8 <strong>Cancer</strong>-Related Autoantigens 22<br />

2.5.9 Non-<strong>Cancer</strong>-Related Autoantigens 23<br />

2.5.10 Products of Underexpressed Genes 23<br />

2.6 Incidence of Antibodies to SEREX Antigens <strong>and</strong> Clinical Significance 23<br />

2.7 Functional Significance of SEREX Antigens 24<br />

2.8 Reverse T Cell Immunology 24<br />

2.9 Towards a Definition of the Human <strong>Cancer</strong> Immunome 24<br />

2.10 Consequences for <strong>Cancer</strong> Vaccine Development 25<br />

2.11 Conclusions <strong>and</strong> Perspectives 26<br />

References 27<br />

3 Processing <strong>and</strong> Presentation of Tumor-associated Antigens 30<br />

Peter-M. Kloetzel <strong>and</strong> Alice Sijts<br />

3.1 The Major Histocompatibility Complex (MHC) Class I Antigen-Processing<br />

Pathway 30<br />

3.2 Immuno-Proteasomes 31<br />

3.2.1 The Function of Immuno-Proteasomes 31<br />

3.2.2 The Role of the Proteasome Activator PA28 in Antigen Processing 33<br />

3.3 The Proteasome System <strong>and</strong> Tumor Antigen Presentation 34<br />

3.3.1 Impaired Epitope Generation <strong>by</strong> Immuno-Proteasomes 35<br />

3.4 PA28 <strong>and</strong> Tumor Epitope Processing 35<br />

3.5 Exploiting Proteasome Knowledge 36<br />

References 37<br />

4 T Cells In Tumor Immunity 40<br />

Pedro Romero, Mikael J. Pittet, Alfred Zippelius, Danielle Li nard,<br />

Ferdy J. Lejeune, Danila Valmori, Daniel E. Speiser <strong>and</strong><br />

Jean-Charles Cerottini<br />

4.1 Introduction 40<br />

4.2 Morphological Evidence of T Cell Immunity in Human Tumors 41<br />

4.3 Approaches to the Molecular Identification of Cytolytic T Lymphocyte<br />

(CTL)-defined Tumor Antigens 41<br />

4.4 Monitoring the Spontaneous CTL Responses to Tumor Antigens 44<br />

4.4.1 Monitoring Specific CTL in the PBMC Compartment 44<br />

4.4.2 Evidence of Tumor Antigen-specific T Cell Responses<br />

at the Tumor Sites 46<br />

4.5 CD4 T Cells in Tumor Immunity 49<br />

4.6 Concluding Remarks 51<br />

References 52

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