Editors' ChoiceCancer

Good Cytokine: Bad Cytokine

Science's STKE  01 Aug 2006:
Vol. 2006, Issue 346, pp. tw255
DOI: 10.1126/stke.3462006tw255

The interplay between the immune system and cancer cells is a complicated one. On the one hand, inflammation associated with tumors is similar to that of protective immune responses and inhibition of responses like turnover of extracellular matrix and angiogenesis, so inhibition of these responses can suppress tumor growth. But immune responses such as the accumulation of tumor-infiltrating T cells are a potent defense mechanism against cancer cells. Can the balance of these effects be altered to enhance therapeutic strategies against cancer? Langowski et al. suggest that signaling by the cytokine interleukin 23 (IL-23) might provide an inroad to such a strategy. IL-23 has beneficial effects in promoting immune responses to bacterial infections. The authors found, however, that expression of IL-23 was increased in samples of human cancer tissues, and its role proved to be not nearly so helpful in fighting off the invading cancer cells. Instead, mice lacking the p19 subunit necessary for formation of the cytokine were resistant to chemical carcinogenesis. Loss of IL-23 was also associated with decreases in several inflammatory effects that contribute to tumor promotion. Furthermore, infiltration of cytotoxic CD8+ T cells--which form a front line of defense in the body's attack on tumor cells--was inhibited by IL-23 and enhanced in its absence. Transplanted tumors grew more poorly in mice that lacked functional IL-23 or its receptor. Thus, the authors conclude that IL-23 is not only ineffective at fighting tumors but actually promotes changes in the tumor environment that enhance or protect tumor growth. This, of course, suggests that therapies to limit IL-23 function may be appropriate new additions to the arsenal of anticancer weapons.

J. L. Langowski, X. Zhang, L. Wu, J. D. Mattson, T. Chen, K. Smith, B. Basham, T. McClanahan, R. A. Kastelein, M. Oft, IL-23 promotes tumour incidence and growth. Nature 442, 461-465 (2006). [PubMed]