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However, their clinical application is constrained by the high incidence of immune-related adverse events (irAEs), which arise from nonspecific immune activation and can affect multiple organ systems, with severe cases posing life-threatening risks. This study integrated high-throughput proteomic and metabolomic analyses to systematically characterize the molecular features associated with irAEs in cancer patients receiving PD-1 inhibitor therapy. The results showed that, following the first treatment, patients who developed irAEs exhibited potential involvement of the NF-\u03baB pathway, along with lower baseline levels of SNRPA and higher expression of CD63. Metabolomic analyses further revealed that the kynurenine\/tryptophan ratio was significantly elevated in the irAE group both at baseline and post-treatment compared with patients who did not develop irAEs. In addition, significant differences in the abundance of specific lipids were observed between the two groups prior to the administration of immunotherapy. Our findings provide exploratory insights into immune and metabolic alterations associated with PD-1 blockade treatment and may help generate hypotheses for future studies on early irAE risk assessment in cancer patients undergoing PD-1 blockade therapy.<\/jats:p>","DOI":"10.1021\/acs.jproteome.6c00421","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T21:22:07Z","timestamp":1788211327000},"page":"4932-4944","source":"Crossref","is-referenced-by-count":0,"title":["Proteomic\nand\nMetabolomic Analysis of Immune-Related\nAdverse Events in Patients Treated with PD-1 Inhibitors"],"prefix":"10.1021","volume":"25","author":[{"given":"Xiaoxuan","family":"Song","sequence":"first","affiliation":[{"name":"Tianjin University , , ,","place":["Tianjin, China, 300072"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanting","family":"Zhou","sequence":"additional","affiliation":[{"name":"Xuanwu Hospital, Capital Medical University , , ,","place":["Beijing, China, 100053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Children\u2019s Hospital , , ,","place":["Tianjin, China, 300074"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gao","sequence":"additional","affiliation":[{"name":"Tianjin University , , ,","place":["Tianjin, China, 300072"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Su","sequence":"additional","affiliation":[{"name":"Tianjin University , , ,","place":["Tianjin, China, 300072"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1149-8049","authenticated-orcid":true,"given":"Ruibing","family":"Chen","sequence":"additional","affiliation":[{"name":"Tianjin University , , ,","place":["Tianjin, China, 300072"]},{"name":"Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency , ,","place":["Tianjin, China, 300072"]},{"name":"State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine (Tianjin Institute of Pharmaceutical Research) , ,","place":["Tianjin, China, 300301"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Li","sequence":"additional","affiliation":[{"name":"Xuanwu Hospital, Capital Medical University , , ,","place":["Beijing, China, 100053"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"issue":"5","key":"2026090409122714100_cit1","doi-asserted-by":"publisher","first-page":"342","DOI":"10.3747\/co.25.4235","article-title":"Immune-related\nadverse events of immune checkpoint inhibitors: a brief review","volume":"25","author":"Myers","year":"2018","journal-title":"Curr. 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Sci."},{"issue":"5","key":"2026090409122714100_cit31","first-page":"367","article-title":"Research progress of kynurenine pathway\nand metabolites and central\nnervous system diseases","volume":"25","author":"Feng","year":"2025","journal-title":"Neurological disorders\nand mental health"},{"issue":"1","key":"2026090409122714100_cit32","doi-asserted-by":"publisher","first-page":"4346","DOI":"10.1038\/s41467-019-12361-9","article-title":"Metabolomic\nadaptations and correlates of survival to immune checkpoint blockade","volume":"10","author":"Li","year":"2019","journal-title":"Nat. Commun."},{"key":"2026090409122714100_cit33","doi-asserted-by":"publisher","first-page":"111412","DOI":"10.1016\/j.intimp.2023.111412","article-title":"Lipidomics reveals\nimmune-related adverse events in\nNSCLC patients receiving immune checkpoint inhibitor","volume":"127","author":"Yu","year":"2024","journal-title":"Int. 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