{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:01:23Z","timestamp":1791820883169,"version":"4.3.4"},"reference-count":32,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Shaanxi province Health Scientific Research","award":["2024TD-14"],"award-info":[{"award-number":["2024TD-14"]}]},{"name":"Research and Development Projects in Shaanxi Province","award":["2025SF-YBXM-338"],"award-info":[{"award-number":["2025SF-YBXM-338"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["12472321"],"award-info":[{"award-number":["12472321"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shaanxi Sanqin Scholars Innovation Team","award":["2021-No.32"],"award-info":[{"award-number":["2021-No.32"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,3,11]]},"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used medications in non-small cell lung cancer (NSCLC). We comprehensively evaluated the effect of NSAID exposure patterns on immunotherapy outcomes, prostaglandin E2 (PGE2) and immune cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter study employed both prospective and retrospective approaches for patient enrollment. Patients were included if they had advanced NSCLC, and were first-time users of immune checkpoint inhibitor (ICI). Endpoints included progression-free survival (PFS) and overall survival (OS). Serum and tumor tissue were collected in the prospective subset for PGE2 and immune cell assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 1,748 patients were included, with 232 patients prospectively enrolled. After multivariable adjustment, NSAID use was independently associated with improved PFS (HR 0.72, 95%\u2009CI 0.58 to 0.91, p=0.0053) and OS (HR=0.76, 95%\u2009CI 0.58 to 0.98, p=0.0364). Benefit was observed for both before-ICI (HR 0.75, 95\u2009% CI 0.57 to 0.99, p=0.0383) and after-ICI initiation (HR 0.63, 95% CI 0.43 to 0.92, p=0.0159). For aspirin, low-dose aspirin users had better PFS than non-users (HR 0.69, 95%\u2009CI 0.51 to 0.94, p=0.0191), especially when used at least 30 days (HR=0.69, 95%\u2009CI 0.48 to 0.99, p=0.0464). Among non-selective NSAIDs, only after-ICI initiation improved OS (HR=0.49, 95%\u2009CI 0.24 to 0.99, p=0.0458). Any-grade (57.8% vs 53.4%)\u2009and grade \u22653 adverse events (9.2% vs 9.8%) were comparable among NSAID users and non-users. Serum sample indicated that aspirin was associated with less PGE2, which was related to better outcomes. On immune cells, RNA-seq revealed a correlation between the cyclooxygenase-2 pathway and neutrophils. Biosample analysis further demonstrated that aspirin use was associated with decreased neutrophils in both circulation and tumor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Long-term low-dose aspirin enhanced immunotherapy efficacy in patients with advanced NSCLC. PGE2 and neutrophils represented potential biomarkers guiding NSAID-immunotherapy integration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05754983\">NCT05754983<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-014360","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T15:40:30Z","timestamp":1775058030000},"page":"e014360","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Impact of NSAID type, initiation timing, duration and dose on clinical outcomes of immunotherapy in NSCLC: a multicenter two-cohort 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