{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:39:29Z","timestamp":1792172369346,"version":"4.4.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"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>Backgroud<\/jats:title>\n                    <jats:p>Ureteritis and cystitis is a rare immune-related adverse event (irAE) of immune checkpoint inhibitors (ICIs), challenging to distinguish from urinary tract infection (UTI), easily leading to missed diagnosis. We aim to describe clinical features, radiological characteristics and treatment of patients who suffer from ICI-related ureteritis and cystitis (ICI-UC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a single centre case series of patients diagnosed with solid tumor who received ICIs treatment and subsequently suffered from ICI-UC. All clinical demographic data, laboratory parameters, imaging characteristics, and treatment information were collected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Between Mar 1\n                      <jats:sup>st<\/jats:sup>\n                      , 2020 and Mar 31\n                      <jats:sup>th<\/jats:sup>\n                      2025, 12 of 1239 patients treated at Peking Union Medical College Hospital with ICIs were confirmed to have ICI-related ureteritis and cystitis (0.96%), 10 males and 2 females. Only 1 patient received anti-programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte associated protein-4 (CTLA-4) dual immunotherapy, the other 11 patients received PD-1\/PD-ligand 1 plus chemotherapy or\/and target therapy. The median time to onset was 83 days (range 28\u2013442 days). All patients (100%) exhibited significant urinary tract irritation symptoms. 12 patients demonstrated characteristic imaging abnormalities, including hydroureteronephrosis, irregular ureteral wall thickening, bladder wall thickening with irregular margins, or\/and conspicuous renal fascia. Spontaneous remission was observed in 2 patients, while 10 patients received steroids and all showed rapid improvement of symptom after treatment.The median time from symptom onset to the initiation of steroids was 24 days, and the median prednisone dose was 0.60 mg\/kg\/day. Six patients (6\/10, 60%) experienced disease recurrence during the corticosteroid tapering phase, and two patients who failed steroid tapering were successfully treated with a combination of corticosteroid and JAK inhibitor therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This pioneering cohort study provides the first systematic investigation of ICI-UC, establishing its incidence and comprehensively characterizing clinical and imaging features. Through cohort analysis, we propose a novel severity grading system with corresponding treatment algorithms, while additionally exploring the therapeutic potential of JAK inhibitors for steroid-dependent cases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1727822","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T06:30:50Z","timestamp":1768890650000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Single-center experience with immune checkpoint inhibitor-related ureteritis and cystitis"],"prefix":"10.3389","volume":"16","author":[{"given":"Chenyu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muwen","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]},{"name":"Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmei","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/s41573-021-00259-5","article-title":"Immune-related toxicities of checkpoint inhibitors: mechanisms and mitigation strategies","volume":"21","author":"Sullivan","year":"2022","journal-title":"Nat Rev Drug Discov"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2020.03.132","article-title":"Immune checkpoint inhibitor-related dermatologic adverse events","volume":"83","author":"Geisler","year":"2020","journal-title":"J Am Acad Dermatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/PAP.0000000000000401","article-title":"Gastrointestinal and hepatobiliary immune-related adverse events: A histopathologic review","volume":"30","author":"Alruwaii","year":"2023","journal-title":"Adv Anat Pathol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s13691-017-0298-6","article-title":"A case of cystitis after administration of nivolumab","volume":"6","author":"Ozaki","year":"2017","journal-title":"Int Cancer Conf J"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.757069","article-title":"Case report: A case of sintilimab-induced cystitis\/ureteritis and review of sintilimab-related adverse events","volume":"11","author":"Tu","year":"2021","journal-title":"Front Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.eucr.2017.12.006","article-title":"Two cases of nonbacterial cystitis associated with nivolumab, the anti-programmed-death-receptor-1 inhibitor","volume":"17","author":"Shimatani","year":"2018","journal-title":"Urol Case Rep"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1226993","article-title":"Immune-related adverse events with severe pain and ureteral expansion as the main manifestations: a case report of tislelizumab-induced ureteritis\/cystitis and review of the literature","volume":"14","author":"Zhou","year":"2023","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/iju5.12211","article-title":"Non-bacterial cystitis with increased expression of programmed death-ligand 1 in the urothelium: An unusual immune-related adverse event during treatment with pembrolizumab for lung adenocarcinoma","volume":"3","author":"Ueki","year":"2020","journal-title":"IJU Case Rep"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3779\/j.issn.1009-3419.2023.106.17","article-title":"Immune checkpoint inhibitors related cystoureteritis: A case report and literature review","volume":"26","author":"Li","year":"2023","journal-title":"Zhongguo Fei Ai Za Zhi."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1051577","article-title":"Immune-related ureteritis and cystitis induced by immune checkpoint inhibitors: Case report and literature review","volume":"13","author":"Li","year":"2022","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0000000000000765","article-title":"Aseptic cystitis induced by nivolumab and ipilimumab combination for metastatic melanoma","volume":"31","author":"Schneider","year":"2021","journal-title":"Melanoma Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0000000000000484","article-title":"Recurrent cystitis associated with 2 programmed death 1 inhibitors: A rare case report and literature review","volume":"46","author":"Fan","year":"2023","journal-title":"J Immunother."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.788629","article-title":"A case report of non-bacterial cystitis caused by immune checkpoint inhibitors","volume":"12","author":"Zhu","year":"2021","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.25486","article-title":"Non-bacterial cystitis with increased expression of programmed cell death ligand 1 in the urothelium: an unusual immune-related adverse event after atezolizumab administration for metastatic breast cancer","volume":"14","author":"Obayashi","year":"2022","journal-title":"Cureus."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/iju5.12532","article-title":"A case of steroid-resistant cystitis as an immune-related adverse event during treatment with nivolumab for lung cancer, which was successfully treated with infliximab","volume":"5","author":"Fukunaga","year":"2022","journal-title":"IJU Case Rep"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-006982","article-title":"Risk factors and immunomodulators use in steroid-refractory checkpoint inhibitor pneumonitis","volume":"11","author":"Li","year":"2023","journal-title":"J Immunother Cancer"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1080\/1750743X.2024.2389761","article-title":"Case reports of immune-related cystitis and the antibody combination hypothesis","volume":"16","author":"Zhang","year":"2024","journal-title":"Immunotherapy"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.55666","article-title":"Acute non-infectious cystitis secondary to immune-related adverse events in a patient receiving pembrolizumab for treatment of non-small cell lung cancer: A case report","volume":"16","author":"Alhusari","year":"2024","journal-title":"Cureus."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S321965","article-title":"Immunotherapy-related cystitis: case report and review of the literature","volume":"14","author":"Zhu","year":"2021","journal-title":"Onco Targets Ther"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1703481","article-title":"Immune-related adverse events associated with immune checkpoint blockade","volume":"378","author":"Postow","year":"2018","journal-title":"N Engl J Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1080\/21691401.2022.2131354","article-title":"Treatment-related adverse events of PD-1\/PD-L1 inhibitors combined with CTLA-4 inhibitors in clinical trials: a meta-analysis","volume":"50","author":"Mi","year":"2022","journal-title":"Artif Cells Nanomed Biotechnol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1167975","article-title":"Immune-related adverse events of immune checkpoint inhibitors: a review","volume":"14","author":"Yin","year":"2023","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-024-00730-3","article-title":"Clinical and translational attributes of immune-related adverse events","volume":"5","author":"Suijkerbuijk","year":"2024","journal-title":"Nat Cancer."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.14362","article-title":"Immune checkpoint inhibitor-related type 1 diabetes incidence, risk, and survival association","volume":"16","author":"Kamitani","year":"2025","journal-title":"J Diabetes Investig"},{"key":"B25","doi-asserted-by":"publisher","first-page":"102536","DOI":"10.1016\/j.eclinm.2024.102536","article-title":"Clinical spectrum and evolution of immune-checkpoint inhibitors toxicities over a decade-a worldwide perspective","volume":"70","author":"Gougis","year":"2024","journal-title":"EClinicalMedicine."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/iju5.12588","article-title":"Successful treatment of immune-related cystitis with bladder hydrodistension","volume":"6","author":"Anraku","year":"2023","journal-title":"IJU Case Rep"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1423123","article-title":"Non-bacterial cystitis caused by pembrolizumab therapy for adenocarcinoma of the lung: a case report","volume":"15","author":"Di","year":"2024","journal-title":"Front Immunol"},{"key":"B28","first-page":"100101","article-title":"A case of severe interstitial cystitis associated with pembrolizumab","volume-title":"Curr Probl Cancer Case Rep.","author":"El Husseini","year":"2021"},{"key":"B29","doi-asserted-by":"publisher","first-page":"100863","DOI":"10.1016\/j.currproblcancer.2022.100863","article-title":"Non-bacterial cystitis secondary to pembrolizumab: A case report and review of the literature","volume":"46","author":"He","year":"2022","journal-title":"Curr Probl Cancer."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1501415","article-title":"Immune-related adverse events with renal colic as the main manifestation: a case report of sintilimab-induced ureteritis\/cystitis treated by ureteral stent and review of the literature","volume":"15","author":"Ji","year":"2024","journal-title":"Front Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1121122","article-title":"Long survival in a pancreatic carcinoma patient with multi-organ toxicities after sintilimab treatment: A case report","volume":"14","author":"Ni","year":"2023","journal-title":"Front Pharmacol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.explore.2022.04.002","article-title":"Successful treatment of immune-related cystitis by Chai-Ling-Tang (Sairei-To) in a gastric carcinoma patient: Case report and literature review","volume":"19","author":"Wang","year":"2023","journal-title":"Explore (NY)."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/iju5.12286","article-title":"Improvement of urinary symptoms after bladder biopsy: A case of pathologically proven allergy-related cystitis during administration of nivolumab","volume":"4","author":"Yajima","year":"2021","journal-title":"IJU Case Rep"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.currproblcancer.2016.12.004","article-title":"Renal complications of immune checkpoint blockade","volume":"41","author":"Murakami","year":"2017","journal-title":"Curr Probl Cancer."},{"key":"B35","article-title":"A case of advanced gastric cancer who experienced multiple immune-related adverse events with nivolumab and SOX therapy","volume":"50","author":"Kihara","year":"2023","journal-title":"Gan To Kagaku Ryoho."},{"key":"B36","first-page":"591","article-title":"Hemorrhagic cystitis: etiology and treatment","volume":"11","author":"Traxer","year":"2001","journal-title":"Prog Urol."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.4137\/CMO.S4477","article-title":"Hemorrhagic cystitis in a patient receiving docetaxel for prostate cancer","volume":"4","author":"Ntekim","year":"2010","journal-title":"Clin Med Insights Oncol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/s13691-016-0255-9","article-title":"A case of hemorrhagic cystitis caused by nab-paclitaxel","volume":"5","author":"Ichioka","year":"2016","journal-title":"Int Cancer Conf J"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v16.i3.1084","article-title":"Hemorrhagic cystitis in gastric cancer after nanoparticle albumin-bound paclitaxel: A case report","volume":"16","author":"Zhang","year":"2024","journal-title":"World J Gastrointest Oncol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/bju.14516","article-title":"Current management of radiation cystitis: a review and practical guide to clinical management","volume":"123","author":"Pascoe","year":"2019","journal-title":"BJU Int"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15051629","article-title":"Predictive biomarkers for checkpoint inhibitor immune-related adverse events","volume":"15","author":"Les","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1908079116","article-title":"Autoimmune antibodies correlate with immune checkpoint therapy-induced toxicities","volume":"116","author":"Tahir","year":"2019","journal-title":"Proc Natl Acad Sci U S A."},{"key":"B43","doi-asserted-by":"publisher","first-page":"e1911519","DOI":"10.1001\/jamanetworkopen.2019.11519","article-title":"Variation in the assessment of immune-related adverse event occurrence, grade, and timing in patients receiving immune checkpoint inhibitors","volume":"2","author":"Hsiehchen","year":"2019","journal-title":"JAMA Netw Open"},{"key":"B44","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41698-023-00380-1","article-title":"Immunosuppression for immune-related adverse events during checkpoint inhibition: an intricate balance","volume":"7","author":"Verheijden","year":"2023","journal-title":"NPJ Precis Oncol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1002\/iju5.12538","article-title":"Editorial Comment to A case of steroid-resistant cystitis as an immune-related adverse event during treatment with nivolumab for lung cancer, which was successfully treated with infliximab","volume":"5","author":"Yuasa","year":"2022","journal-title":"IJU Case Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1727822\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T12:27:55Z","timestamp":1770812875000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1727822\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,20]]},"references-count":45,"alternative-id":["10.3389\/fimmu.2025.1727822"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1727822","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,20]]},"article-number":"1727822"}}