Mouse pulmonary interstitial macrophages mediate the pro-tumorigenic effects of IL-9.

Abstract

Although IL-9 has potent anti-tumor activity in adoptive cell transfer therapy, some models suggest that it can promote tumor growth. Here, we show that IL-9 signaling is associated with poor outcomes in patients with various forms of lung cancer, and is required for lung tumor growth in multiple mouse models. CD4+ T cell-derived IL-9 promotes the expansion of both CD11c+ and CD11c- interstitial macrophage populations in lung tumor models. Mechanistically, the IL-9/macrophage axis requires arginase 1 (Arg1) to mediate tumor growth. Indeed, adoptive transfer of Arg1+ but not Arg1- lung macrophages to Il9r-/- mice promotes tumor growth. Moreover, targeting IL-9 signaling using macrophage-specific nanoparticles restricts lung tumor growth in mice. Lastly, elevated expression of IL-9R and Arg1 in tumor lesions is associated with poor prognosis in lung cancer patients. Thus, our study suggests the IL-9/macrophage/Arg1 axis is a potential therapeutic target for lung cancer therapy.

• Authors: Yongyao Fu, Abigail Pajulas, Jocelyn Wang, Baohua Zhou, Anthony Cannon, Cherry Cheuk Lam Cheung, Jilu Zhang, Huaxin Zhou, Amanda Jo Fisher, David T Omstead, Sabrina Khan, Lei Han, Jean-Christophe Renauld, Sophie Paczesny, Hongyu Gao, Yunlong Liu, Lei Yang, Robert M Tighe, Paula Licona-Limón, Richard A Flavell, Shogo Takatsuka, Daisuke Kitamura, Jie Sun, Basar Bilgicer, Catherine R Sears, Kai Yang, Mark H Kaplan
• Journal: Nature communications (Nat Commun) Vol. 13 Issue 1 Pg. 3811 (07 01 2022) ISSN: 2041-1723 [Electronic] England
• PMID: 35778404 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• IL9 protein, human
• Interleukin-9

Topics

• Animals
• Carcinogenesis (metabolism)
• Interleukin-9 (genetics, metabolism)
• Lung Neoplasms (metabolism, pathology)
• Macrophages (metabolism, pathology)
• Macrophages, Alveolar (metabolism)
• Mice