{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T18:03:05Z","timestamp":1786903385511,"version":"build-2736575974"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T00:00:00Z","timestamp":1706486400000},"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><jats:title>Background<\/jats:title><jats:p>Immunotherapy, represented by immune checkpoint inhibitors (ICIs), is a major breakthrough in cancer treatment. Studies have reported that the use of ICIs is associated with an increase in the pulmonary artery to ascending aorta diameter (PAD\/AoD) ratio. However, the impact of PAD\/AoD ratio progression on the prognosis of patients is unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This retrospective cohort study included patients with stage III or IV non-small cell lung cancer (NSCLC) treated with ICIs at the Wuhan Union Hospital between March 1, 2020, and September 1, 2022. The baseline and post-treatment PAD\/AoD ratios of patients were evaluated through chest CT scans. The primary outcome of this study was overall survival (OS), while the secondary outcomes included progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The PAD\/AoD ratio increased after the initiation of ICIs (from 0.75 to 0.78; <jats:italic>P<\/jats:italic> &amp;lt; 0.001). A total of 441 patients were divided into severe group (n=221) and non-severe group (n=220) according to the median increase of PAD\/AoD ratio (1.06). Compared with the non-severe group, the severe group had a lower DCR (87.8% vs. 96.0%, <jats:italic>P<\/jats:italic> = 0.005) and ORR (87.5% vs. 96.0%, <jats:italic>P<\/jats:italic> = 0.063). Over the entire duration of follow-up (median 22.0 months), 85 (38.5%) patients in the severe group and 30 (7.3%) patients in the non-severe group died. An increased PAD\/AoD ratio was associated with shorter PFS (Hazard ratio (HR): 1.48 [95% CI, 1.14 to 1.93]; <jats:italic>P<\/jats:italic> = 0.003) and OS (HR: 3.50 [95% CI, 2.30 to 5.30]; <jats:italic>P<\/jats:italic> &amp;lt; 0.001). Similar results were obtained across subgroups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ICI treatment exacerbates an increase in the PAD\/AoD ratio in patients with cancer, and greater increase in the PAD\/AoD ratio was associated with a worse prognosis. PAD\/AoD ratio could be a biomarker to stratify prognosis of NSCLC patients treated with ICIs.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1302233","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T04:20:38Z","timestamp":1706502038000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["The impact of pulmonary artery to ascending aorta diameter ratio progression on the prognosis of NSCLC patients treated with immune checkpoint inhibitors"],"prefix":"10.3389","volume":"15","author":[{"given":"Bingxin","family":"Gong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusheng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guofeng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyu","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0066","article-title":"Genomic approaches to understanding response and resistance to immunotherapy","volume":"22","author":"Braun","year":"2016","journal-title":"Clin Cancer Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar4060","article-title":"Cancer immunotherapy using checkpoint blockade","volume":"359","author":"Ribas","year":"2018","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00312-3","article-title":"Lung cancer","volume":"398","author":"Thai","year":"2021","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J Clin"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716078","article-title":"Neoadjuvant PD-1 blockade in resectable lung cancer","volume":"378","author":"Forde","year":"2018","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.07.011","article-title":"Neoadjuvant immune checkpoint blockade: A window of opportunity to advance cancer immunotherapy","volume":"41","author":"Topalian","year":"2023","journal-title":"Cancer Cell"},{"key":"B7","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s12943-023-01740-y","article-title":"Lung cancer immunotherapy: progress, pitfalls, and promises","volume":"22","author":"Lahiri","year":"2023","journal-title":"Mol Cancer"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2022.01.001","article-title":"Immune-related adverse events in various organs caused by immune checkpoint inhibitors","volume":"71","author":"Okiyama","year":"2022","journal-title":"Allergol Int"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2023.2221434","article-title":"Updates in toxicities associated with immune checkpoint inhibitors","volume":"19","author":"Curkovic","year":"2023","journal-title":"Expert Rev Clin Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1094414","article-title":"Immune checkpoint inhibitor-associated toxicity in advanced non-small cell lung cancer: An updated understanding of risk factors","volume":"14","author":"Hu","year":"2023","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-0091","article-title":"At the heart of immune checkpoint inhibitor-induced immune toxicity","volume":"11","author":"Young","year":"2021","journal-title":"Cancer Discovery"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0000000000000895","article-title":"Pulmonary adverse events following immune checkpoint inhibitors","volume":"28","author":"Spagnolo","year":"2022","journal-title":"Curr Opin Pulm Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"5403","DOI":"10.3390\/cancers14215403","article-title":"Cardiotoxicity induced by immune checkpoint inhibitors: what a cardio-oncology team should know and do","volume":"14","author":"Zito","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.22034\/iji.2023.96898.2464","article-title":"Pulmonary arterial hypertension induced by immune checkpoint inhibitor combined therapy in a patient with intrahepatic cholangiocarcinoma: A case report","volume":"20","author":"Zhang","year":"2023","journal-title":"Iran J Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2045894020960967","DOI":"10.1177\/2045894020960967","article-title":"Releasing the brakes: a case report of pulmonary arterial hypertension induced by immune checkpoint inhibitor therapy","volume":"10","author":"Glick","year":"2020","journal-title":"Pulm Circ"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacr.2022.09.018","article-title":"ACR appropriateness criteria\u00ae Suspected pulmonary hypertension: 2022 update","volume":"19","author":"Sirajuddin","year":"2022","journal-title":"J Am Coll Radiol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1097\/00005382-199910000-00007","article-title":"A CT sign of chronic pulmonary arterial hypertension: the ratio of main pulmonary artery to aortic diameter","volume":"14","author":"Ng","year":"1999","journal-title":"J Thorac Imaging"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.09090548","article-title":"Detection of pulmonary hypertension with multidetector CT and echocardiography alone and in combination","volume":"254","author":"Devaraj","year":"2010","journal-title":"Radiology"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-21-0786","article-title":"Clinical effect of pulmonary artery diameter\/ascending aorta diameter ratio on left ventricular reverse remodeling in patients with dilated cardiomyopathy","volume":"86","author":"Shibata","year":"2022","journal-title":"Circ J"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.2147\/COPD.S131413","article-title":"Pulmonary artery to aorta ratio is associated with cardiac structure and functional changes in mild-to-moderate COPD","volume":"12","author":"Cuttica","year":"2017","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.8605-21","article-title":"Pulmonary artery diameter (PAD) and the pulmonary artery to aorta ratio (PAD\/AAD) as assessed by non-contrast cardiac CT: the association with left ventricular (LV) remodeling and the LV function","volume":"61","author":"Nguyen-Thu","year":"2022","journal-title":"Internal Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2045894021992236","DOI":"10.1177\/2045894021992236","article-title":"Adverse effects of immune checkpoint inhibitor therapies on right ventricular function and pulmonary arterial dilatation","volume":"11","author":"Mylvaganam","year":"2021","journal-title":"Pulm Circ"},{"key":"B23","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1007\/s00280-020-04142-9","article-title":"Nivolumab increases pulmonary artery pressure in patients treated for non-small cell lung cancer","volume":"86","author":"Fournel","year":"2020","journal-title":"Cancer Chemotherapy Pharmacol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"497","DOI":"10.6004\/jnccn.2022.0025","article-title":"Non-small cell lung cancer, version 3.2022, NCCN clinical practice guidelines in oncology","volume":"20","author":"Ettinger","year":"2022","journal-title":"J Natl Compr Canc Netw"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1203830","article-title":"Pulmonary arterial enlargement and acute exacerbations of COPD","volume":"367","author":"Wells","year":"2012","journal-title":"N Engl J Med"},{"key":"B26","doi-asserted-by":"publisher","first-page":"244","DOI":"10.3390\/nu14020244","article-title":"The association of dietary intake with arterial stiffness and vascular ageing in a population with intermediate cardiovascular risk-A MARK study","volume":"14","author":"G\u00f3mez-S\u00e1nchez","year":"2022","journal-title":"Nutrients"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr130","article-title":"Iron deficiency is associated with adverse outcome in Eisenmenger patients","volume":"32","author":"Van De Bruaene","year":"2011","journal-title":"Eur Heart J"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2015.10.003","article-title":"Prognostic value of lymphocyte-to-monocyte ratio in patients with solid tumors: A systematic review and meta-analysis","volume":"41","author":"Nishijima","year":"2015","journal-title":"Cancer Treat Rev"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s00595-019-01954-y","article-title":"Impact of the preoperative bone mineral density on the outcomes after resection of pancreatic cancer","volume":"50","author":"Sharshar","year":"2020","journal-title":"Surg Today"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdp357","article-title":"Insulin-like growth factor receptor 1 (IGF1R) expression and survival in surgically resected non-small-cell lung cancer (NSCLC) patients","volume":"21","author":"Cappuzzo","year":"2010","journal-title":"Ann Oncol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz406","article-title":"Interfering with long non-coding RNA MIR22HG processing inhibits glioblastoma progression through suppression of Wnt\/\u03b2-catenin signalling","volume":"143","author":"Han","year":"2020","journal-title":"Brain"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur J Cancer"},{"key":"B33","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/s41572-020-0160-6","article-title":"Immune-related adverse events of checkpoint inhibitors","volume":"6","author":"Ramos-Casals","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.312513","article-title":"Atlas of the immune cell repertoire in mouse atherosclerosis defined by single-cell RNA-sequencing and mass cytometry","volume":"122","author":"Winkels","year":"2018","journal-title":"Circ Res"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0590-4","article-title":"Single-cell immune landscape of human atherosclerotic plaques","volume":"25","author":"Fernandez","year":"2019","journal-title":"Nat Med"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.001347","article-title":"Cytotoxic and proinflammatory CD8+ T lymphocytes promote development of vulnerable atherosclerotic plaques in apoE-deficient mice","volume":"127","author":"Kyaw","year":"2013","journal-title":"Circulation"},{"key":"B37","doi-asserted-by":"publisher","first-page":"j5492","DOI":"10.1136\/bmj.j5492","article-title":"Pulmonary arterial hypertension: pathogenesis and clinical management","volume":"360","author":"Thenappan","year":"2018","journal-title":"Bmj"},{"key":"B38","doi-asserted-by":"publisher","first-page":"3757","DOI":"10.3390\/jcm10163757","article-title":"Role of the immune system elements in pulmonary arterial hypertension","volume":"10","author":"Tomaszewski","year":"2021","journal-title":"J Clin Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.312058","article-title":"Dominant role for regulatory T cells in protecting females against pulmonary hypertension","volume":"122","author":"Tamosiuniene","year":"2018","journal-title":"Circ Res"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s00380-015-0727-4","article-title":"Non-suppressive regulatory T cell subset expansion in pulmonary arterial hypertension","volume":"31","author":"Sada","year":"2016","journal-title":"Heart Vessels"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1130438","article-title":"Advances in immune checkpoint inhibitors induced-cardiotoxicity","volume":"14","author":"Li","year":"2023","journal-title":"Front Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2019.01.038","article-title":"Cardio-oncology - strategies for management of cancer-therapy related cardiovascular disease","volume":"280","author":"Totzeck","year":"2019","journal-title":"Int J Cardiol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"5529","DOI":"10.1038\/s41467-023-41066-3","article-title":"Fasting mimicking diet in mice delays cancer growth and reduces immunotherapy-associated cardiovascular and systemic side effects","volume":"14","author":"Cortellino","year":"2023","journal-title":"Nat Commun"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000000256","article-title":"CT-base pulmonary artery measurement in the detection of pulmonary hypertension: a meta-analysis and systematic review","volume":"93","author":"Shen","year":"2014","journal-title":"Med (Baltimore)"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2018.07.006","article-title":"Ratio of pulmonary artery diameter to ascending aortic diameter and severity of heart failure","volume":"37","author":"Chimura","year":"2018","journal-title":"J Heart Lung Transplant"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s10554-019-01548-2","article-title":"Computed tomography-measured pulmonary artery to aorta ratio and EUTOS score for detecting dasatinib-induced pulmonary arterial hypertension","volume":"35","author":"Toya","year":"2019","journal-title":"Int J Cardiovasc Imaging"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1138483","article-title":"Immune-related pulmonary toxicities of checkpoint inhibitors in non-small cell lung cancer: Diagnosis, mechanism, and treatment strategies","volume":"14","author":"Guo","year":"2023","journal-title":"Front Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-022-03208-2","article-title":"Pulmonary hypertension reported with immune checkpoint inhibitors: a pharmacovigilance study","volume":"71","author":"Palassin","year":"2022","journal-title":"Cancer Immunology Immunotherapy"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1302233\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T04:20:44Z","timestamp":1706502044000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1302233\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,29]]},"references-count":48,"alternative-id":["10.3389\/fimmu.2024.1302233"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1302233","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,29]]},"article-number":"1302233"}}