{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:53:34Z","timestamp":1782917614031,"version":"3.54.5"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare subtype of non-small cell lung cancer characterized by pronounced regional clustering and high PD-L1 expression. Although early studies suggest that first-line immunotherapy combined with chemotherapy has application potential, we still lack large-sample systematic reviews and cross-high-incidence-area real-world validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The electronic databases were systematically searched from inception until January 31, 2026. Studies comparing first-line immunotherapy combined with chemotherapy versus chemotherapy alone in patients with advanced primary pulmonary lymphoepithelioma-like carcinoma (PLELC) were included. To validate the findings, an independent multicenter real-world cohort was concurrently incorporated. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Stata 15.0 and R software (utilizing inverse probability of treatment weighting [IPTW]) were used to synthesize the meta-analysis and adjust the real-world cohort data, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The initial meta-analysis (encompassing 606 patients) demonstrates that adding PD-1\/PD-L1 inhibitors to chemotherapy significantly prolongs both progression-free survival (PFS) and overall survival (OS) without elevating the risk of severe adverse events. Within the independent multicenter cohort from Guangxi, the combination therapy group continues to display a profound PFS benefit after IPTW strictly balances the baseline disease burden (18.0 vs. 6.5 months, HR\u00a0=\u00a00.17, P &amp;lt; 0.001). OS in this cohort exhibits a protective trend (HR\u00a0=\u00a00.85); however, incorporating this real-world effect size into the global meta-model yields updated pooled data that further reinforces its robust, cross-regional survival advantage (PFS HR\u00a0=\u00a00.42; OS HR\u00a0=\u00a00.51). Multivariate prognostic analysis identifies baseline liver metastasis as an independent risk factor for reduced OS, whereas PD-L1 positivity significantly correlates with improved PFS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This integrated systematic review and multicenter real-world cohort study suggests the superior efficacy and safety of first-line chemoimmunotherapy over chemotherapy alone, providing evidence-based support for the management of advanced PPLELC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1872713","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:13:20Z","timestamp":1782915200000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of first-line chemoimmunotherapy versus chemotherapy alone for advanced pulmonary lymphoepithelioma-like carcinoma: a systematic review and real-world cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Feng","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiandong","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Hematology, Red Cross Hospital of Yulin City","place":["Yulin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology, Guangxi Medical University Cancer Hospital","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuye","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Affiliated Hospital of Youjiang Medical University For Nationalities","place":["Baise, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi rao","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyuan","family":"Cen","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, 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