{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:02:38Z","timestamp":1790960558684,"version":"4.1.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T00:00:00Z","timestamp":1718582400000},"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. Pharmacol."],"abstract":"<jats:p>\n                    <jats:bold>Introduction:<\/jats:bold>\n                    An increasing number of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) have been reported during clinical treatment. We aimed to explore the clinical characteristics of patients with ICIs-induced ITP under different therapeutic strategies based on the FAERS database and explore the potential biological mechanisms in combination with TCGA pan-cancer data.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Data from FAERS were collected for ICIs adverse reactions between January 2012 and December 2022. Disproportionality analysis identified ICIs-induced ITP in the FAERS database using the reporting odds ratio (ROR), proportional reporting ratio (PRP), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker algorithms (MGPS). The potential biological mechanisms underlying ITP induced by ICIs were examined using TCGA transcriptome data on cancers.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    In the FAERS, 345 ICIs-induced ITP reports were retrieved, wherein 290 (84.06%) and 55 (15.94%) were reported as monotherapy and combination therapy, respectively. The median age of the reported patients with ICIs-induced ITP was 69 years (IQR 60-76), of which 62 (18%) died and 47 (13.6%) had a life-threatening outcome. The majority of reported indications were lung, skin, and bladder cancers, and the median time to ITP after dosing was 42 days (IQR 17-135), with 64 patients (43.5%) experiencing ITP within 30 days of dosing and 88 patients experiencing ITP in less than 2\u00a0months (59.9%). The occurrence of ICIs-induced ITP may be associated with ICIs-induced dysregulation of the mTORC1 signaling pathway and megakaryocyte dysfunction.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    There were significant reporting signals for ITP with nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab\/ipilimumab, and pembrolizumab\/ipilimumab. Patients treated with anti-PD-1 in combination with anti-CTLA-4 are more likely to have an increased risk of ICIs-induced ITP. Patients with melanoma are at a higher risk of developing ITP when treated with ICI and should be closely monitored for this risk within 60 days of treatment. The potential biological mechanism of ICIs-induced ITP may be related to the dysfunction of megakaryocyte autophagy through the overactivation of the mTOR-related signaling pathway. This study provides a comprehensive understanding of ICIs-induced ITP. Clinicians should pay attention to this potentially fatal adverse reaction.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2024.1407894","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T00:42:38Z","timestamp":1718584958000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Association of thrombocytopenia with immune checkpoint inhibitors: a large-scale pharmacovigilance analysis based on the data from FDA adverse event reporting system database"],"prefix":"10.3389","volume":"15","author":[{"given":"Geliang","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuechun","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peifeng","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1186\/s13059-017-1349-1","article-title":"xCell: digitally portraying the tissue cellular heterogeneity landscape","volume":"18","author":"Aran","year":"2017","journal-title":"Genome Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1093\/annonc\/mdm170","article-title":"Akt-induced endocrine therapy resistance is reversed by inhibition of mTOR signaling","volume":"18","author":"Beeram","year":"2007","journal-title":"Ann. 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