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We evaluated the heterogeneity in PD-L1 expression in the primary lung site and metastatic lymph nodes to analyze the association between PD-L1 expression and response for patients treated with EGFR-TKI.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This study reviewed 184 advanced NSCLC patients with EGFR mutations who received first-generation EGFR-TKI as first-line treatment from 2020 to 2021 at Shanghai Chest Hospital. The patients were divided into the primary lung site group (<jats:italic>n<\/jats:italic>\u2009=\u2009100) and the metastatic lymph nodes group (<jats:italic>n<\/jats:italic>\u2009=\u200984) according to the biopsy site. The patients in each group were divided into TPS\u2009&lt;\u20091%, TPS 1\u201349%, and TPS\u2009\u2265\u200950% groups according to PD-L1 expression.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The median PFS was 7 (95% CI: 5.7\u20138.3) months, and the median OS was 26 (95% CI: 23.5\u201328.5) months for all patients. No correlation existed between PFS or OS and PD-L1 expression. The median PFS in the primary lung site group was 11 months (95% CI: 9.6\u201312.4) in the TPS\u2009&lt;\u20091% group, 8 months (95% CI: 6.6\u20139.4) in TPS 1\u201349% group, and 4 months (95% CI: 3.2\u20134.8) in TPS\u2009\u2265\u200950% group, with statistically significant differences (<jats:italic>p<\/jats:italic>\u2009=\u20090.000). The median OS of the TPS\u2009&lt;\u20091% group and TPS\u2009\u2265\u200950% group showed a statistically significant difference (<jats:italic>p<\/jats:italic>\u2009=\u20090.008) in the primary lung site group. In contrast, PD-L1 expression in the lymph nodes of EGFR-mutant patients was unrelated to PFS or OS after EGFR-TKI therapy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>PD-L1 expression from the primary lung site might predict clinical benefit from EGFR-TKI, whereas PD-L1 from metastatic lymph nodes did not.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>: This retrospective study was approved by the Ethics Committee of Shanghai Chest Hospital (ID: IS23060) and performed following the Helsinki Declaration of 1964 (revised 2008).<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12931-024-02858-3","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T04:01:42Z","timestamp":1717560102000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Heterogeneity in PD-L1 expression between primary and metastatic lymph nodes: a predictor of EGFR-TKI therapy response in non-small cell lung cancer"],"prefix":"10.1186","volume":"25","author":[{"given":"Yaohua","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingqi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7535-0740","authenticated-orcid":false,"given":"Lei","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4616-1224","authenticated-orcid":false,"given":"Runbo","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,5]]},"reference":[{"key":"2858_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21708","volume":"72","author":"RL Siegel","year":"2022","unstructured":"Siegel RL, Miller KD, Fuchs HE, Jemal A. 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