Concepts and Ways to Amplify the Antitumor Immune Response

Bent Rubin and Jean Edouard Gairin

Contents

1 Introduction 98

2 Pharmacology of Tumor Cell-Immune Cell Interactions 100

3 Tumor Cell Development and Its Danger Signals 101

3.1 Neoplastic Cells 102

3.2 Chronic Inflammation 103

3.3 Stroma 105

4 Expression and Presentation of Tumor Antigens 105

5 Mouse Models of Cancer 107

5.1 The LCMV Model to Study the Regulation of MHCI Expression 107

5.2 The L12R4 Vaccination Model 109

5.3 The SR/CR Mouse Model 110

6 Cellular and Molecular Regulation of Tumor Immunity 113

7 Discussion 117

References 122

Abstract In this chapter, a detailed description of how the innate and adaptive immune responses interact with malignant cells is presented. In addition, we discuss how developing tumors establish themselves, and how they benefit on one hand and organize their defense against the immune system on the other hand. New data from three tumor model systems in mice are discussed; in particular, the intricate interactions between the immune cells and the tumor cells are highlighted. With the present data and knowledge, we conclude that a first prerequisite for the

B. Rubin

Institut de Sciences et Technologies du Médicament de Toulouse, UMR 2587 CNRS-Pierre Fabre, 3, rue des Satellites, 31400 Toulouse, France J.E. Gairin (*)

Institut de Sciences et Technologies du Medicament de Toulouse, UMR 2587 CNRS-Pierre Fabre, 3, rue des Satellites, 31400 Toulouse, France

Faculte de Pharmacie, Universite Paul Sabatier, 31400 Toulouse, France e-mail: [email protected]

G. Dranoff (ed.), Cancer Immunology and Immunotherapy, 97

Current Topics in Microbiology and Immunology 344, DOI 10.1007/82_2010_89 © Springer-Verlag Berlin Heidelberg 2011, published online: 3 August 2010

combat against tumors is the activation of the innate immune system via external danger signals or damage signals and internal danger signals. The second prerequisite for efficient tumor cell eradication is combined therapeutic approaches of physical, chemical, pharmacological, and immunological origin. Finally, we propose new ways for further investigation of the relationship linking tumor cells and our defense system. It appears mandatory to understand how the malignant cells render the adaptive immune cells tolerant instead of turning them into aggressive effectors and memory cells. Perhaps, the most important thing, for immunologists and clinicians, to understand is that tumor cells must not be viewed just as antigens but much more.

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