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

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204 Cancer Immune Therapie: Current and Future Strategies Edited by G. Stuhler and P. Walden Copyright # 2002 Wiley-VCH Verlag GmbH & Co. KGaA ISBNs: 3-527-30441-X (Hardback); 3-527-60079-5 (Electronic) 10 The Immune System in Cancer: If It Isn't Broken, Can We Fix It? Dragan Terremovic and Richard G. Vile 10.1 Commitment and the Modern Immune System The importance of immune effector cells in protecting against the emergence of tumors within immunocompetent hosts has been a point of controversy for many years. In the 1970s, Burnet proposed that lymphocytes patrol the body and react to, and remove, tumor cells that have escaped normal controls of growth and differentiation, giving rise to the concept of ªcancer immunosurveillanceº [1]. However, this attractive (and comforting) theory became less credible with the observation that athymic nude mice, lacking functional T cells, develop tumors at the same rate as their immunocompetent wild-type counterparts. To understand these competing views better, it is important to realize that immune recognition of tumors is only one of the roles that the modern immune system has evolved to fulfill. Probably higher on its list of priorities comes its ability to recognize and respond to invading pathogens. However, along with this need for vigorous reactivity against non-self antigens, comes an equally important need to ignore self antigens (see Appendix). Hence, the modern immune system is constantly pulled in opposite directions with stringent twin requirements of aggressive responses against infectious foreign pathogens whilst maintaining a complete lack of response to self antigens to avoid autoimmunity. Within the confines of these two extremes is the need to deal with the threat posed by the uncontrolled growth and dissemination of cancer cells. In order to understand how the immune system should evolve to be able to meet all of the demands that are asked of it, let us consider the two extreme models (Fig. 10.1). In one model (Fig. 10.1A), immune recognition of tumors might have become finely tuned to recognize all emerging tumor cells and the molecular mutations associated with them. A second option, erring on the side of preventing autoimmune disease, would be an immune system that has no capacity to respond to emerging tumor cells at all (Fig. 10.1B). In reality, the most likely situation, which offers maximal benefit to the species, falls between these two extremes of immunological hypersensitivity and immunological ignorance (Fig. 10.1).
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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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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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98 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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Page 185 and 186: 150 7 Immunosuppresive Factors in C
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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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