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Trends Immunol. 2007 May;28(5):207-12. Epub 2007 Mar 28.

Swords into plowshares: IL-23 repurposes tumor immune surveillance.

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  • 1Schering-Plough BioPharma, 901 California Avenue, Palo Alto, CA 94304, USA.

Abstract

During tumorigenesis, selective pressure drives tumor cells to develop several strategies that enable growth and propagation. Transformed cells produce or elicit factors that provide growth signals, nutrients and a favorable tumor microenvironment. In addition, tumor cells can evade elimination by the immune system by several mechanisms, including developing resistance to T cell-induced apoptosis or the local expression of immune-modulatory molecules and cytokines. Recently, we described a role for the cytokine interleukin (IL)-23 in promoting tumor incidence and growth. In addition, IL-23 not only stimulates neutrophil and macrophage infiltration, but also promotes angiogenesis and inflammatory mediators in the tumor microenvironment. IL-23 antagonizes IL-12 and interferon gamma, both of which are essential cytokines for cytotoxic immune responses, and controls the influx and activity of anti-tumor effector lymphocytes. We suggest that IL-23 inflicts a repurposing of the adaptive cytotoxic effector response away from anti-tumor immunity ('sword') and towards proinflammatory and proangiogenic effector pathways that nourish the tumor ('plowshare'). Consequently, IL-23 enables the persistence of the recognized tumor cells, accompanied by tumor-associated inflammation. This concept can explain tumor growth in the presence of large quantities of tumor-specific T cells.

PMID:
17395538
DOI:
10.1016/j.it.2007.03.006
[PubMed - indexed for MEDLINE]
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