{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:30:58Z","timestamp":1789605058153,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21ck0106673h0001"],"award-info":[{"award-number":["21ck0106673h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Serum growth\/differentiation factor 15 (GDF\u201015) suppresses anti\u2010tumor immunity and predicts prognosis in several malignancies. Elevated GDF\u201015 levels are linked to cancer cachexia, characterized by weight loss and systemic inflammation, adversely affecting patient outcomes and therapy response. However, serum GDF\u201015 is not always derived from tumor tissues but also from multiple organs. Therefore, we evaluated whether intra\u2010tumoral GDF\u201015 could be used as a biomarker for immunotherapy and its potential association with cancer cachexia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We retrospectively evaluated patients with advanced non\u2010small cell lung cancer (NSCLC) who underwent treatment with programmed cell death\u20101 (PD\u20101)\/programmed cell death\u2010ligand 1 (PD\u2010L1) inhibitors at the Shizuoka Cancer Center between 2017 and 2021. Patients with histologically confirmed NSCLC (stage III\u2013IV or postoperative recurrence) who had undergone biopsy or surgery within 6\u2009months prior to initiating immunotherapy were included. Expression of tumor\u2010derived GDF\u201015 was evaluated using immunohistochemical staining of archival biopsy and surgical specimens. We analyzed the correlation between intra\u2010tumoral GDF\u201015 expression and the incidence of cancer cachexia, as well as its impact on progression\u2010free survival (PFS) and overall survival (OS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>In 6 of 35 cases, tumor cells highly expressed GDF\u201015. Patients with high intra\u2010tumoral GDF\u201015 expression had a higher incidence of cancer cachexia (100% vs. 41.4%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), shorter PFS (3.4 vs. 13.4\u2009months, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), and shorter OS (9.5 vs. 26.5\u2009months, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) than those with low intra\u2010tumoral GDF\u201015 expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Intra\u2010tumoral GDF\u201015 expression may predict the presence of cancer cachexia and the efficacy of PD\u20101\/PD\u2010L1 inhibitors in patients with advanced non\u2010small cell lung cancer.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1759-7714.70089","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T11:14:52Z","timestamp":1747826092000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Desensitizing Effect of Intra\u2010Tumoral <scp>GDF<\/scp>\u201015 on Immunotherapy in Patients With Advanced Non\u2010Small Cell\u00a0Lung Cancer"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6938-4976","authenticated-orcid":false,"given":"Naoya","family":"Nishioka","sequence":"first","affiliation":[{"name":"Division of Thoracic Oncology Shizuoka Cancer Center  Shizuoka Japan"},{"name":"Department of Pulmonary Medicine Graduate School of Medical Science, Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4047-2929","authenticated-orcid":false,"given":"Tateaki","family":"Naito","sequence":"additional","affiliation":[{"name":"Division of Thoracic Oncology Shizuoka Cancer Center  Shizuoka Japan"},{"name":"Division of Cancer Supportive Care Center Shizuoka Cancer Center  Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Sugino","sequence":"additional","affiliation":[{"name":"Division of Pathology Shizuoka Cancer Center  Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Muramatsu","sequence":"additional","affiliation":[{"name":"Division of Pathology Shizuoka Cancer Center  Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeki","family":"Nishihara","sequence":"additional","affiliation":[{"name":"Department of CNS Research Otsuka Pharmaceutical Co., Ltd.  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