{"id":59122,"date":"2026-03-18T13:03:48","date_gmt":"2026-03-18T12:03:48","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/03\/18\/macrophage-intrinsic-and-il-9-dependent-arginine-metabolism-promotes-lung-tumor-growth\/"},"modified":"2026-03-18T13:03:48","modified_gmt":"2026-03-18T12:03:48","slug":"macrophage-intrinsic-and-il-9-dependent-arginine-metabolism-promotes-lung-tumor-growth","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/03\/18\/macrophage-intrinsic-and-il-9-dependent-arginine-metabolism-promotes-lung-tumor-growth\/","title":{"rendered":"Macrophage-intrinsic and IL-9-dependent arginine metabolism promotes lung tumor growth"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2026 Mar 17;215(3):vkag026. doi: 10.1093\/jimmun\/vkag026.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Tumor-associated macrophages are an abundant, tumor-infiltrating cell population that supports the evasion of tumor cells from antitumoral immune cell detection by generating an immunosuppressive tumor-immune microenvironment (TIME). The immunosuppressive function of macrophages is dictated by the cytokine environment. IL-9 is a pleiotropic cytokine that can be a positive or negative regulator of tumor growth. Our lab previously identified a protumoral role of IL-9 by expanding lung interstitial macrophage (IM) populations and inducing the expression of arginase 1 (ARG1) to enhance tumor growth. However, the underlying mechanism by which IL-9 receptor\/ARG1+ IMs promote tumor progression remains incomplete. Here, we demonstrate that macrophage-targeting nanoparticles containing Arg1 siRNA can therapeutically reduce tumor burden and reduce protumor arginine-derived metabolite production. Furthermore, using bulk RNA sequencing of lung macrophages isolated from Il9r-\/-:wild-type mixed-bone marrow chimeric mice, we demonstrate that IL-9 intrinsically alters the transcriptomic landscape of lung IMs. Mechanistically, IL-9 promotes intrinsic Arg1 expression through an IRF4-dependent regulatory pathway and modulates arginine and polyamine concentration within IMs and lung tissue, resulting in increased lung tumor growth and altered macrophage phenotypes. Thus, our work defines a protumor function of IL-9-responsive macrophages mediated by altered intrinsic arginine metabolism in lung IMs that enhances lung tumor growth.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41847865\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20260318080335&amp;v=2.19.0.post6+133c1fe\">41847865<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkag026\">10.1093\/jimmun\/vkag026<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2026 Mar 17;215(3):vkag026. doi: 10.1093\/jimmun\/vkag026. ABSTRACT Tumor-associated macrophages are an abundant, tumor-infiltrating cell population that supports the evasion of tumor cells from antitumoral immune cell detection by generating an immunosuppressive tumor-immune microenvironment (TIME). The immunosuppressive function of macrophages is dictated by the cytokine environment. IL-9 is a pleiotropic cytokine that can be a &#8230; <a title=\"Macrophage-intrinsic and IL-9-dependent arginine metabolism promotes lung tumor growth\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/03\/18\/macrophage-intrinsic-and-il-9-dependent-arginine-metabolism-promotes-lung-tumor-growth\/\" aria-label=\"Read more about Macrophage-intrinsic and IL-9-dependent arginine metabolism promotes lung tumor growth\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-59122","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/59122","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=59122"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/59122\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=59122"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=59122"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=59122"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}