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. 2012 May 1;1(3):351-354.
doi: 10.4161/onci.19122.

Interleukin-21 in cancer immunotherapy: Friend or foe?

Carmine Stolfi  1 , Francesco Pallone, Thomas T Macdonald, Giovanni Monteleone
Affiliations

Interleukin-21 in cancer immunotherapy: Friend or foe?

Carmine Stolfi et al. Oncoimmunology. .

Abstract

Interleukin (IL)-21, a cytokine produced by activated conventional CD4+ T lymphocytes and Natural Killer T cells, drives anti-tumor immunity in the skin and kidney. However IL-21 is also pro-inflammatory in many tissues and promotes colitis-associated colon cancer. Understanding the biology of IL-21 in these different situations is needed to ensure maximal therapeutic benefit.

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Figures

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Figure 1. Putative functions of IL-21 in promoting colitis-associated colon cancer. In normal intestine APC-driven T cell activation is counter-regulated by Tregs. During inflammation, activated T cells produce increased level of IL-21 that damps Treg differentiation and, in parallel, promotes T cell expansion and subsequent secretion of pro-tumorigenic cytokines (e.g., IL-6 and IL-17A). These cytokines target DNA mutation-sensitized epithelial cells promoting their proliferation through STAT3 activation and fostering tumor development. Finally, tumor-infiltrating cells sustain and amplify this pro-tumoral milieu by secreting IL-21, IL-6 and IL-17A.
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