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 t

SUBMITTER: Fu Y 

PROVIDER: S-EPMC9249769 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature