Itaconate: A metabolic intermediate with an impact on tumors<\/strong><\/p>\n Itaconate is produced primarily by macrophages \u2013 immune cells that are also found in tumor tissue, where they can perform different and sometimes opposing functions. In lung cancer tissue, the researchers found significantly lower levels of itaconate than in adjacent non-tumorous lung tissue. Single-cell analyses also showed that macrophages are the main cells in the tumor tissue expressing IRG1, the enzyme responsible for itaconate production.<\/p>\n The researchers investigated the significance of this finding for tumor growth using several experimental models. When IRG1 was knocked out, or when mice were treated with bone marrow cells deficient in IRG1, they developed larger lung tumors. Conversely, treatment with the itaconate derivative 4-octyl itaconate inhibited tumor growth in cell culture, animal models, and human tumor tissue.<\/p>\n G6PD as a key target<\/strong><\/p>\n Using integrated metabolic and gene expression analyses, the team identified an important mechanism underlying this effect. Itaconate affects the pentose phosphate pathway, a central metabolic pathway involved in providing reducing equivalents and building blocks required for cell growth. G6PD, an enzyme acting at the beginning of this pathway, plays a key role. The researchers found that IRG1 and itaconate inhibit G6PD activity. In the absence of IRG1, by contrast, G6PD activity increases in tumor tissue. The study therefore directly links the immune response of macrophages to tumor cell metabolism.<\/p>\n Itaconate acts on both immune cells and tumor cells<\/strong><\/p>\n A particularly interesting aspect is that the mechanism operates on two levels. First, itaconate affects the macrophages themselves. When IRG1 levels are reduced in these immune cells, their metabolism and functional state change: the cells show fewer features associated with an anti-tumor response and acquire more pro-tumor characteristics. Targeted inhibition of G6PD was able to partially reverse these changes.<\/p>\n Second, itaconate acts directly on cancer cells. By inhibiting G6PD and the pentose phosphate pathway, it restricts a metabolic process that is important for tumor cells, thereby slowing their growth. The researchers describe this as both a cell-autonomous effect in macrophages and a direct, non-cell-autonomous effect on tumor cells.<\/p>\n Findings confirmed in human tumor tissue<\/strong><\/p>\n In addition to cell culture and animal models, the team investigated the effects of itaconate in human lung cancer tissue. Among other approaches, the researchers used so-called precision-cut lung slices<\/em> \u2013 thin tissue sections that partially preserve the complex tumor environment outside the body. In this model, 4-octyl itaconate also reduced tumor growth. The analysis of human tumor samples was conducted with appropriate informed consent and ethical approval.<\/p>\n A potential avenue for future therapies<\/strong><\/p>\n The findings make the itaconate\u2013G6PD metabolic pathway an interesting target for further lung cancer research. In particular, the effects of 4-octyl itaconate open up a potential therapeutic perspective. However, clinical application in humans is still a long way off. The current study is preclinical. The researchers also point out that 4-octyl itaconate differs from endogenous itaconate in terms of pharmacokinetics and distribution in the body. Direct measurements of itaconate concentrations and G6PD activity in patients are also still lacking.<\/p>\n The study therefore primarily provides new insights into the close interplay between the immune system, metabolism, and tumor growth, while highlighting a potential avenue for exploiting this connection therapeutically in the future.<\/p>\n Schematic illustration of the IRG1\/itaconate\u2013G6PD signaling pathway in lung cancer. Itaconate produced by macrophages inhibits the metabolic enzyme G6PD, thereby affecting the metabolism and function of immune cells. At the same time, itaconate acts directly on tumor cells, where it inhibits metabolism, nucleotide production, and cell proliferation. In this way, the mechanism helps limit lung tumor growth.<\/em><\/p>\n Original publication:<\/strong> Mansouri S, Hesami G, Ambikan A, Karger A, Klatt S, Neogi U, Kurakula KB, Aliraj B, Miller A, Petrova B, Sanda M, Sirait-Fischer E, Guenther S, Kuenne C, Ruppert C, Alkoudmani I, Gattenl\u00f6hner S, Zukunft S, Fleming I, Haschemi A, Stiewe T, Grimminger F, Reck M, Weigert A, Seeger W, Pullamsetti SS, Savai R. IRG1\/itaconate rewires macrophage and lung tumor metabolism through G6PD inhibition.<\/em> Cell Metab. 2026 Jul 7;38(7):1460\u20131477.e8. doi: 10.1016\/j.cmet.2026.05.005<\/a>. Epub 2026 Jun 3. PMID: 42235511.<\/p>\n","protected":false},"excerpt":{"rendered":" DZL researchers have elucidated a previously poorly understood mechanism of tumor regulation: itaconate, a metabolic intermediate produced by certain immune cells, can influence the metabolism of lung cancer cells and tumor-associated macrophages, thereby inhibiting tumor growth.<\/p>\n","protected":false},"author":26,"featured_media":59074,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","_seopress_robots_follow":"","_seopress_robots_imageindex":"","_seopress_robots_snippet":"","_seopress_robots_primary_cat":"","_seopress_robots_breadcrumbs":"","_seopress_robots_freeze_modified_date":"","_seopress_robots_custom_modified_date":"","_seopress_robots_canonical":"","_seopress_social_fb_title":"","_seopress_social_fb_desc":"","_seopress_social_fb_img":"","_seopress_social_fb_img_attachment_id":0,"_seopress_social_fb_img_width":0,"_seopress_social_fb_img_height":0,"_seopress_social_twitter_title":"","_seopress_social_twitter_desc":"","_seopress_social_twitter_img":"","_seopress_social_twitter_img_attachment_id":0,"_seopress_social_twitter_img_width":0,"_seopress_social_twitter_img_height":0,"_seopress_redirections_value":"","_seopress_redirections_enabled":"","_seopress_redirections_enabled_regex":"","_seopress_redirections_logged_status":"","_seopress_redirections_param":"","_seopress_redirections_type":0,"_seopress_analysis_target_kw":"","footnotes":""},"categories":[28],"tags":[286,246],"class_list":["post-59075","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","tag-biobanking-data-management-platform","tag-lung-cancer-lc"],"acf":[],"_links":{"self":[{"href":"https:\/\/dzl.de\/en\/wp-json\/wp\/v2\/posts\/59075","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/dzl.de\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/dzl.de\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/dzl.de\/en\/wp-json\/wp\/v2\/users\/26"}],"replies":[{"embeddable":true,"href":"https:\/\/dzl.de\/en\/wp-json\/wp\/v2\/comments?post=59075"}],"version-history":[{"count":3,"href":"https:\/\/dzl.de\/en\/wp-json\/wp\/v2\/posts\/59075\/revisions"}],"predecessor-version":[{"id":59078,"href":"https:\/\/dzl.de\/en\/wp-json\/wp\/v2\/posts\/59075\/revisions\/59078"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/dzl.de\/en\/wp-json\/wp\/v2\/media\/59074"}],"wp:attachment":[{"href":"https:\/\/dzl.de\/en\/wp-json\/wp\/v2\/media?parent=59075"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/dzl.de\/en\/wp-json\/wp\/v2\/categories?post=59075"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/dzl.de\/en\/wp-json\/wp\/v2\/tags?post=59075"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}![\"\"](\"https:\/\/dzl.de\/wp-content\/uploads\/2026\/09\/1-s2.0-S1550413126001907-ga1_lrg-300x300.jpg\")
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