Subversion and Coercion The Art of Redirecting Tumor Immune Surveillance

John B. Mumm and Martin Oft

Contents

1 Introduction 26

2 The Inflammatory Trio: TNF-a, TGF-b, IL-6 28

3 The Local Trigger: IL-23 and IL-12 Balance in the Tumor Microenvironment 30

4 Feeding the Inflammatory Niche: Adaptive T Cell

Responses Fostering the Tumor 31

5 Turning Foes into Friends, CD8+ T Cells Lose Their Teeth 32

6 Inflammatory Control at the Tumor Site 33

7 Conclusions 35

References 36

Abstract Tumor immune surveillance and CD8+ T cells in particular appear capable of recognizing the antigenic properties of human tumor cells. However, those antigen specific T cells are often excluded from tumor tissue or are functionally limited in their cytotoxic capacity. Instead, the immune response provides proinflammatory cytokines and proteases promoting tumor growth and progression while subverting cytotoxic anti-tumor immunity. The cytokines and the inflammatory mechanisms driving tumor associated inflammation resemble tissue remodeling processes during wound healing and chronic inflammatory diseases. In this chapter, we summarize the current knowledge of how inflammatory cytokines may promote the deviation of anti-tumor immunity toward a tumor promoting, noncy-totoxic inflammation.

Merck Research Labs (formerly DNAX) 901 California Avenue, Palo Alto, CA 94303, USA e-mail: [email protected]

G. Dranoff (ed.), Cancer Immunology and Immunotherapy, 25

Current Topics in Microbiology and Immunology 344, DOI 10.1007/82_2010_47 © Springer-Verlag Berlin Heidelberg 2011, published online: 19 May 2010

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