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

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Fig. 5.12 Correlation between the level of TAP and MHC class I expression with progression and survival time (according to Kageshita et al. [61]). Deficient MHC class I and TAP expression significantly correlates with the progression of disease as well as survival time. 5.5 The Different MHC Class I Phenotypes and their Underlying Molecular Mechanisms 73
74 5 Major Histocompatibility Complex Modulation and Loss Fig. 5.13 Representative examples of defects in HLA class I antigen expression in surgically removed carcinoma lesions of distinct origin. Frozen tissue sections were stained in the immunoperoxidase reaction with respective anti-HLA class I mAbs. (Top panels) The lack of staining of the breast carcinoma lesions in the right top panel by the anti-HLA-A, -B and -C mAbs indicates a total HLA class I antigen loss in this lesion. (Middle panels) The lack of staining of the lesion with an anti-HLA-B mAb indicates a selective loss of the gene products of HLA-B loci. (Bottom panels) The lack of staining of the lesion with the anti-HLA-A30 mAb indicates selective loss of the HLA class I allospecificity. (see color plates page XXII) MHC class Iabnormalities might be missed if the different MHC molecules potentially expressed on the cell surface are not independently measured. There exist distinct mechanisms resulting in allele- or locus-specific decrease or loss of MHC class Iantigens. Loss of one MHC class Ihaplotype associated with LOH at chromosome 6p21 has been described in cell lines derived from melanoma, colon carcinoma, pancreatic carcinoma and cervical carcinoma lesions [33, 67±71] (Tab. 5.3). This altered MHC class Iphenotype can be easily and reproducibly detected by microsatellite marker analysis using PCR amplification. A representative example is shown in Fig. 5.14 for a colon carcinoma cell line. This phenotype is caused by loss of variable portions of genomic DNA which is attributable to chromosomal segregation, non-dysjunction or mitotic recombination in the short arm of chromosome 6, where the MHC region has been mapped [72]. The frequency of haplotype loss in tumors derived from different tissues has not yet been evaluated in de- Tab. 5.3 HLA haplotype loss: LOH at 6p21 Tumor cell line Tumor References FM55 melanoma 149 FM37 melanoma IMIM-PC2 pancreatic carcinoma 68 NW145 melanoma 150 OCM-3 uveal melanoma 154 877 cervical carcinoma 157 CC-11 cervical carcinoma 155
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Cancer Immune Therapie: Current and
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Editors: Dr. Gernot Stuhler Univers
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VI Preface Recent years have seen a
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VIII Contents 2.5.3 Antigens Encode
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X Contents 6.4.2 Natural Killer (NK
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XII Contents 9.6 Loading DC with An
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XIV Contents 14.2.2.1 Cancer-specif
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List of Contributors Richard Bucala
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Color Plates Fig. 5.2 The MHC class
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Fig. 5.5 Different immune effector
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Fig. 5.17 Possible pathway for the
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Fig. 6.2 T lymphocytes in the tumor
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Index a acidic and basic fibroblast
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±, see also tumors cationic lipids
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e EBV see Epstein-Barr virus EDR se
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immature Mo-DCs 184 immune cells ±
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MHC class I antigen-processing mach
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±, onco- 209 ±, over-expressed ce
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TICD see tumor-induced cell death T
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Part 1 Tumor Antigenicity Cancer Im
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4 1 Search for Universal Tumor-Asso
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10 1 Search for Universal Tumor-Ass
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18 2 Serological Determinants On Tu
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Page 79 and 80: 42 4 T Cells In Tumor Immunity cult
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Page 157 and 158: 122 7 Immunosuppresive Factors in C
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124 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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204 Cancer Immune Therapie: Current
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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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