{"id":7564,"date":"2021-07-07T14:56:31","date_gmt":"2021-07-07T12:56:31","guid":{"rendered":"https:\/\/semmelweis.hu\/bioinformatika\/?p=7564"},"modified":"2021-10-04T15:00:32","modified_gmt":"2021-10-04T13:00:32","slug":"megjelent-uj-cikkunk-a-science-translational-medicine-folyoiratban","status":"publish","type":"post","link":"https:\/\/semmelweis.hu\/bioinformatika\/megjelent-uj-cikkunk-a-science-translational-medicine-folyoiratban\/","title":{"rendered":"Megjelent \u00faj cikk\u00fcnk a SCIENCE TRANSLATIONAL MEDICINE foly\u00f3iratban"},"content":{"rendered":"<h1 style=\"text-align: center\"><span style=\"font-size: 18pt\">Down-regulation of A20 promotes immune escape of lung adenocarcinomas<\/span><\/h1>\n<p>SCIENCE TRANSLATIONAL MEDICINE\u20227 Jul 2021\u2022<span class=\"core-enumeration\">Vol\u00a013<span class=\"delimiter\">,\u00a0<\/span>Issue\u00a0601<\/span><\/p>\n<p><a href=\"https:\/\/doi.org\/10.1126\/scitranslmed.abc3911\">10.1126\/scitranslmed.abc3911<\/a><\/p>\n<h2>Abstract<\/h2>\n<div role=\"paragraph\">Inflammation is a well-known driver of lung tumorigenesis. One strategy by which tumor cells escape tight homeostatic control is by decreasing the expression of the potent anti-inflammatory protein tumor necrosis factor alpha\u2013induced protein 3 (TNFAIP3), also known as A20. We observed that tumor cell intrinsic loss of A20 markedly enhanced lung tumorigenesis and was associated with reduced CD8<sup>+<\/sup>\u00a0T cell\u2013mediated immune surveillance in patients with lung cancer and in mouse models. In mice, we observed that this effect was completely dependent on increased cellular sensitivity to interferon-\u03b3 (IFN-\u03b3) signaling by aberrant activation of TANK-binding kinase 1 (TBK1) and increased downstream expression and activation of signal transducer and activator of transcription 1 (STAT1). Interrupting this autocrine feed forward loop by knocking out IFN-\u03b1\/\u03b2 receptor completely restored infiltration of cytotoxic T cells and rescued loss of A20 depending tumorigenesis. Downstream of STAT1, programmed death ligand 1 (PD-L1) was highly expressed in A20 knockout lung tumors. Accordingly, immune checkpoint blockade (ICB) treatment was highly efficient in mice harboring A20-deficient lung tumors. Furthermore, an A20 loss-of-function gene expression signature positively correlated with survival of melanoma patients treated with anti\u2013programmed cell death protein 1. Together, we have identified A20 as a master immune checkpoint regulating the TBK1\u2013STAT1\u2013PD-L1 axis that may be exploited to improve ICB therapy in patients with lung adenocarcinoma.<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Down-regulation of A20 promotes immune escape of lung adenocarcinomas SCIENCE TRANSLATIONAL MEDICINE\u20227 Jul 2021\u2022Vol\u00a013,\u00a0Issue\u00a0601 <a href=\"https:\/\/doi.org\/10.1126\/scitranslmed.abc3911\">10.1126\/scitranslmed.abc3911<\/a> Abstract Inflammation is a well-known driver of lung tumorigenesis. One strategy by which tumor cells escape tight homeostatic control is by decreasing the expression of the potent anti-inflammatory protein tumor necrosis factor alpha\u2013induced protein 3 (TNFAIP3), also known as A20. We &hellip;<\/p>\n","protected":false},"author":101779,"featured_media":7566,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2],"tags":[],"class_list":["post-7564","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-hirek"],"acf":[],"_links":{"self":[{"href":"https:\/\/semmelweis.hu\/bioinformatika\/wp-json\/wp\/v2\/posts\/7564","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/semmelweis.hu\/bioinformatika\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/semmelweis.hu\/bioinformatika\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/semmelweis.hu\/bioinformatika\/wp-json\/wp\/v2\/users\/101779"}],"replies":[{"embeddable":true,"href":"https:\/\/semmelweis.hu\/bioinformatika\/wp-json\/wp\/v2\/comments?post=7564"}],"version-history":[{"count":1,"href":"https:\/\/semmelweis.hu\/bioinformatika\/wp-json\/wp\/v2\/posts\/7564\/revisions"}],"predecessor-version":[{"id":7565,"href":"https:\/\/semmelweis.hu\/bioinformatika\/wp-json\/wp\/v2\/posts\/7564\/revisions\/7565"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/semmelweis.hu\/bioinformatika\/wp-json\/wp\/v2\/media\/7566"}],"wp:attachment":[{"href":"https:\/\/semmelweis.hu\/bioinformatika\/wp-json\/wp\/v2\/media?parent=7564"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/semmelweis.hu\/bioinformatika\/wp-json\/wp\/v2\/categories?post=7564"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/semmelweis.hu\/bioinformatika\/wp-json\/wp\/v2\/tags?post=7564"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}