{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:08:17Z","timestamp":1791943697442,"version":"4.3.4"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102022\u2010NR071926"],"award-info":[{"award-number":["RS\u20102022\u2010NR071926"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002635","name":"Inha University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002635","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICIs) have limited benefit in epidermal growth factor receptor (EGFR)\u2010mutant non\u2010small cell lung cancer (NSCLC). However, they are often tried after tumors develop resistance to EGFR tyrosine kinase inhibitors (TKIs). Because EGFR\u2010TKI treatment alters the tumor microenvironment, biomarkers predictive of ICI response are ideally identified post\u2010EGFR\u2010TKI resistance, but obtaining repeat biopsies at this time can be challenging. The purpose of this study was to explore predictive biomarkers for ICI response using plasma samples collected after EGFR\u2010TKI therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective analysis included 28 patients with EGFR\u2010mutant NSCLC treated with an ICI after developing resistance to EGFR\u2010TKI. Plasma samples collected at TKI progression were profiled using an Olink Target 96 immune protein panel to identify differential protein expression. Candidate protein biomarkers were validated by immunohistochemistry in tumor tissue. Durable clinical response (DCB) was defined as patients achieving progression\u2010free survival (PFS)\u2009\u2265\u20096\u2009months during ICI therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 28 patients, 6 (21.4%) achieved durable clinical benefit, with PFS \u2265\u20096\u2009months. Proteomic analysis identified four plasma proteins that differed significantly between DCB and NCB. Gal\u20109 and GZMH levels were elevated in NCB, whereas IL\u20104 and IL\u20106 were elevated in DCB. Notably, PFS was significantly longer in patients with lower Gal\u20109 and higher IL\u20104 levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Plasma\u2010based immune markers measured at the time of TKI resistance may help predict which patients with EGFR\u2010mutant NSCLC will respond to subsequent ICI therapy. Such biomarkers could guide immunotherapy decision\u2010making in this clinically challenging population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1759-7714.70257","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T01:10:59Z","timestamp":1773450659000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Blood Based Biomarkers for Predicting Treatment Response to Immune Checkpoint Inhibitors After\n                    <scp>EGFR<\/scp>\n                    \u2010\n                    <scp>TKI<\/scp>\n                    Resistance in Non\u2010Small Cell Lung Cancer"],"prefix":"10.1111","volume":"17","author":[{"given":"Min Seok","family":"Park","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences College of Medicine, Inha University  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5515-737X","authenticated-orcid":false,"given":"Jun Hyeok","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Pulmonology, Department of Internal Medicine Inha University Hospital, Inha University College of Medicine  Incheon Republic of Korea"},{"name":"Yonsei University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuri","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences College of Medicine, Inha University  Incheon Republic of Korea"},{"name":"Division of Pulmonology, Department of Internal Medicine Inha University Hospital, Inha University College of Medicine  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunji","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences College of Medicine, Inha University  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayoung","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences College of Medicine, Inha University  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suji","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences College of Medicine, Inha University  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yejin","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences College of Medicine, Inha University  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sehan","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences College of Medicine, Inha University  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minseo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine Inha University College of Medicine  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghyun","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Medicine Inha University College of Medicine  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology Inha University Hospital, Inha University College of Medicine  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Kyung","family":"Ryu","sequence":"additional","affiliation":[{"name":"Division of Pulmonology, Department of Internal Medicine Inha University Hospital, Inha University College of Medicine  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong\u2010Seon","family":"Ryu","sequence":"additional","affiliation":[{"name":"Division of Pulmonology, Department of Internal Medicine Inha University Hospital, Inha University College of Medicine  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine Yonsei University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soon\u2010Sun","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences College of Medicine, Inha University  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Hee","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences 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