{"id":57041,"date":"2026-02-26T00:53:49","date_gmt":"2026-02-25T23:53:49","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/02\/26\/loss-of-mir-29a-b1-cluster-reprograms-the-tumor-microenvironment-and-contributes-to-immunosuppression-in-lung-cancer\/"},"modified":"2026-02-26T00:53:49","modified_gmt":"2026-02-25T23:53:49","slug":"loss-of-mir-29a-b1-cluster-reprograms-the-tumor-microenvironment-and-contributes-to-immunosuppression-in-lung-cancer","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/02\/26\/loss-of-mir-29a-b1-cluster-reprograms-the-tumor-microenvironment-and-contributes-to-immunosuppression-in-lung-cancer\/","title":{"rendered":"Loss of miR-29a\/b1 cluster reprograms the tumor microenvironment and contributes to immunosuppression in lung cancer"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2026 Feb 25. doi: 10.1158\/2326-6066.CIR-25-1060. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Immune checkpoint inhibitors (ICI), including those that block PD-1\/PD-L1, have revolutionized therapy for patients with non-small cell lung cancer. However, most patients demonstrate no clinical benefit or acquire resistance, even when tumors express PD-L1. This highlights the critical need to dissect tumor survival dependencies to overcome resistance. Using our Kras\/p53-driven lung cancer models that demonstrate acquired or intrinsic resistance to ICI, we performed single-cell RNA sequencing and focused on predicted upstream regulators of differentially expressed genes in the malignant cell cluster of resistant tumors. We found that the micro-RNA miR-29 was downregulated in tumors with anti-PD-1 resistance, and that this was associated with significant upregulation of a multitude of miR-29 targets. Furthermore, we found expression of Enpp2\/ATX, a gene encoding an immunosuppressive molecule, was modulated due to miR-29 loss. Re-expression of miR-29 in anti-PD-1 resistant models reduced ATX expression in tumor cells, diminished the fibrotic microenvironment, and increased CD8+ T-cell infiltration. These alterations promoted response to ICI in an anti-PD-1 resistant model by rewiring the tumor immune microenvironment, specifically through increased CD8+ T-cell infiltration, reduction of suppressive Ly6C+ monocytes, and a concomitant increase in pro-inflammatory macrophages. Additional analysis of publicly available RNA-sequencing data revealed tumors from lung adenocarcinoma patients with high miR-29 had increased CD8A and decreased CD14 expression, and broad enrichment in immunoregulatory pathways. Together, these data provide evidence that the miR-29 family regulates the tumor microenvironment, including antitumor immune-related pathways in lung cancer, through control of ATX among other target genes, with implications for ICI response.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41739590\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20260225185340&amp;v=2.18.0.post22+67771e2\">41739590<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-1060\">10.1158\/2326-6066.CIR-25-1060<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2026 Feb 25. doi: 10.1158\/2326-6066.CIR-25-1060. Online ahead of print. ABSTRACT Immune checkpoint inhibitors (ICI), including those that block PD-1\/PD-L1, have revolutionized therapy for patients with non-small cell lung cancer. However, most patients demonstrate no clinical benefit or acquire resistance, even when tumors express PD-L1. This highlights the critical need to dissect tumor &#8230; <a title=\"Loss of miR-29a\/b1 cluster reprograms the tumor microenvironment and contributes to immunosuppression in lung cancer\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/02\/26\/loss-of-mir-29a-b1-cluster-reprograms-the-tumor-microenvironment-and-contributes-to-immunosuppression-in-lung-cancer\/\" aria-label=\"Read more about Loss of miR-29a\/b1 cluster reprograms the tumor microenvironment and contributes to immunosuppression in lung cancer\">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":[55,42],"tags":[],"class_list":["post-57041","post","type-post","status-publish","format-standard","hentry","category-cancer-immunology-reserch","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/57041","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=57041"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/57041\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=57041"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=57041"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=57041"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}