{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:27:21Z","timestamp":1791224841000,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>EGFR<\/jats:italic>\n                    \u2010mutant lung adenocarcinoma (LUAD) is typically associated with an immunosuppressive tumor immune microenvironment (TIME) and poor responses to PD\u20101 blockade. However, the contribution of drug\u2010tolerant persister cells (DTPs) to immunotherapy resistance remains unclear. We hypothesized that DTPs\u2010derived chemokine (C\u2010C motif) ligand 20 (CCL20) promotes immune evasion and impairs PD\u20101\u2010based immunotherapy in\n                    <jats:italic>EGFR<\/jats:italic>\n                    \u2010mutant. To test this, humanized NSG mice engrafted with\n                    <jats:italic>EGFR<\/jats:italic>\n                    \u2010mutant H1975 cells and human peripheral blood mononuclear cells (\n                    <jats:italic>n<\/jats:italic>\n                    = 6 per group) were administered with anti\u2010PD\u20101 (200\u00a0\u00b5g) and\/or anti\u2010CCL20 (20\u00a0\u00b5g) every other day for a total of four doses. The combination reduced mean tumor volume by 65% compared with control treatment (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.01). Single\u2010cell RNA sequencing showed that cotreatment selectively suppressed\n                    <jats:italic>CCL20<\/jats:italic>\n                    expression in DTP clusters and activated interferon\u2010\u03b1 and \u2010\u03b3 signaling (ISG15, CMPK2). Multiplex immunofluorescence revealed combination treatment increased infiltration of M1\u2010like macrophages, plasmacytoid dendritic cells, and memory B cells, alongside spatial segregation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    regulatory T cells (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05). These findings identify DTPs\u2010derived CCL20 as a mediator of immunosuppressive TIME and support combined CCL20\/PD\u20101 blockade as a potential therapeutic strategy for\n                    <jats:italic>EGFR<\/jats:italic>\n                    \u2010mutant lung adenocarcinoma.\n                  <\/jats:p>","DOI":"10.1002\/mco2.70888","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T08:54:51Z","timestamp":1785747291000},"source":"Crossref","is-referenced-by-count":1,"title":["CCL20 Released by Drug\u2013Tolerant Persisters Impairs Immunotherapy in\n                    <i>EGFR\u2013<\/i>\n                    Mutant Lung Adenocarcinoma"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6902-8402","authenticated-orcid":false,"given":"Hoi\u2010Hin","family":"Kwok","sequence":"first","affiliation":[{"name":"Department of Medicine Li Ka Shing Faculty of Medicine University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiashuang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medicine Li Ka Shing Faculty of Medicine University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerissa Chui\u2010Mei","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine Li Ka Shing Faculty of Medicine University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyang","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Medicine Li Ka Shing Faculty of Medicine University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Chi\u2010Leung","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Medicine Li Ka Shing Faculty of Medicine University of Hong Kong  Hong Kong SAR 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