title: Swords into plowshares: IL-23 repurposes tumor immune surveillance.
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.
authors: Schering-Plough BioPharma, 901 California Avenue, Palo Alto, CA 94304, USA.
authors: John L
authors: JL
authors: Langowski
authors: Robert A
authors: RA
authors: Kastelein
authors: Martin
authors: M
authors: Oft
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D007157:Immunologic Surveillance; D007249:Inflammation / Q000473:pathology*; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000098:blood supply / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000276:immunology
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23