{"id":63333,"date":"2026-05-06T01:22:49","date_gmt":"2026-05-05T23:22:49","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/05\/06\/uba2-high-osteosarcoma-suppresses-immune-infiltration-by-autophagy-mediated-mhc-i-degradation\/"},"modified":"2026-05-06T01:22:49","modified_gmt":"2026-05-05T23:22:49","slug":"uba2-high-osteosarcoma-suppresses-immune-infiltration-by-autophagy-mediated-mhc-i-degradation","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/05\/06\/uba2-high-osteosarcoma-suppresses-immune-infiltration-by-autophagy-mediated-mhc-i-degradation\/","title":{"rendered":"UBA2-High Osteosarcoma Suppresses Immune Infiltration by Autophagy-Mediated MHC-I Degradation"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2026 May 5. doi: 10.1158\/2326-6066.CIR-25-1321. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Osteosarcoma (OS) responds poorly to immune-checkpoint blockade (ICB), and the molecular drivers of its immune-cold state remain unclear. Using multi-omics analyses, we identified an immune-cold OS subtype characterized by enrichment of protein SUMOylation and found the SUMO E1 subunit UBA2 as a key driver. UBA2 was anomalously upregulated in OS cohorts and linked to worse outcomes. Functionally, UBA2 promoted autophagy, thereby exerting noncanonical pro-tumor and immunosuppressive effects. Mechanistically, UBA2 catalyzed SUMO2-dependent SUMOylation of SESN2, enhancing autophagic flux. At the immune interface, UBA2 did not alter the expression of immune checkpoint molecules but reduced surface MHC-I through NBR1-mediated autophagy-lysosomal degradation, thereby limiting CD8\u207a T-cell infiltration. In vivo, pharmacologic UBA2 inhibition with ML-792 slowed tumor growth and sensitized tumors to ICB therapy. Together, these findings show that UBA2 links SUMOylation to autophagy-driven loss of antigen presentation and immune exclusion, highlighting the UBA2-autophagy-MHC-I axis as a therapeutic target and potential biomarker in OS.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42085301\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20260505192249&amp;v=2.19.0.post6+133c1fe\">42085301<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-1321\">10.1158\/2326-6066.CIR-25-1321<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2026 May 5. doi: 10.1158\/2326-6066.CIR-25-1321. Online ahead of print. ABSTRACT Osteosarcoma (OS) responds poorly to immune-checkpoint blockade (ICB), and the molecular drivers of its immune-cold state remain unclear. Using multi-omics analyses, we identified an immune-cold OS subtype characterized by enrichment of protein SUMOylation and found the SUMO E1 subunit UBA2 as a &#8230; <a title=\"UBA2-High Osteosarcoma Suppresses Immune Infiltration by Autophagy-Mediated MHC-I Degradation\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/05\/06\/uba2-high-osteosarcoma-suppresses-immune-infiltration-by-autophagy-mediated-mhc-i-degradation\/\" aria-label=\"Read more about UBA2-High Osteosarcoma Suppresses Immune Infiltration by Autophagy-Mediated MHC-I Degradation\">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-63333","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\/63333","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=63333"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/63333\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=63333"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=63333"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=63333"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}