{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T07:00:39Z","timestamp":1785308439594,"version":"3.55.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006595","name":"Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii","doi-asserted-by":"publisher","award":["PN-IV-P2-2.1-TE-2023-1182"],"award-info":[{"award-number":["PN-IV-P2-2.1-TE-2023-1182"]}],"id":[{"id":"10.13039\/501100006595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related death, with most patients diagnosed at advanced, unresectable stages. Although immune-checkpoint inhibitors have transformed the therapeutic landscape, only a subset of patients achieves meaningful and sustained benefit. In this context, circulating soluble immune-checkpoints, particularly soluble PD-L1 (sPD-L1) have emerged as promising non-invasive biomarkers with potential prognostic and predictive value.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To clarify their relevance, we conducted a systematic review and meta-analysis of studies published between 2015 and 2025, evaluating the association between serum levels of these biomarkers and clinical outcomes in NSCLC. A total of 20 studies including 1967 patients were analyzed, despite heterogeneity in study design and treatment regimens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Lower baseline sPD-L1 levels consistently correlated with longer progression-free (PFS: random effect model with a pooled HR of 2.26 [95% CI: 1.77-2.87, p &amp;lt; 0.0001]) and overall survival (OS: random effect model with a pooled HR of 2.04 [95% CI 1.55-2.68, p &amp;lt; 0.0001]), whereas elevated concentrations were frequently observed in males, smokers, individuals with advanced disease, and those with liver metastases. Associations between soluble checkpoints and tumor histology, mutational status, or tissue PD-L1 expression varied widely across studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overall, our findings highlight baseline sPD-L1 with a median cut-off of 90 pg\/mL as a promising prognostic biomarker for PFS in NSCLC, suggesting that dynamic monitoring combined with clinical and molecular parameters could enhance patient stratification. Prospective, standardized studies are needed to define optimal cut-offs and validate clinical utility across treatment settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1896427","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:03:17Z","timestamp":1785304997000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Soluble immune checkpoints in lung cancer: linking prognostic signatures to immunotherapy response \u2013 a meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Larisa-Maria","family":"Rotariu","sequence":"first","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodora","family":"Alexa-Stratulat","sequence":"additional","affiliation":[{"name":"Grigore T. 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