{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T09:36:25Z","timestamp":1780652185828,"version":"3.54.1"},"reference-count":62,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T00:00:00Z","timestamp":1775347200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100015377","name":"Shanghai Key Laboratory of Molecular Imaging","doi-asserted-by":"publisher","award":["18DZ2260400"],"award-info":[{"award-number":["18DZ2260400"]}],"id":[{"id":"10.13039\/501100015377","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012600","name":"ShanghaiTech University","doi-asserted-by":"publisher","award":["2013F0301\u2010000\u201006"],"award-info":[{"award-number":["2013F0301\u2010000\u201006"]}],"id":[{"id":"10.13039\/501100012600","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2021MH291"],"award-info":[{"award-number":["ZR2021MH291"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Immune checkpoint inhibitors (ICIs) universally enhance antitumor immunity but endanger a subgroup of patients by triggering immune\u2010related adverse events (irAEs). We profiled the expressions of 41 proteins on peripheral blood mononuclear cells (PBMCs) prior the initiation of immunotherapy. CXCR3 and CCR6 expressions were significantly decreased in PBMC subpopulations from patient with irAEs but not from those who responded to PD\u20101 inhibitors. The expression of CCR6 in a NK cell subpopulation serves exclusively as a biomarker to differentiate patients who developed irAEs. Interestingly, circulating ligands of CXCR3, including CXCL9, CXCL10, and CXCL11, were significantly increased in patients who later developed irAEs after PD\u20101 inhibitor treatment. The decreases of CXCR3 in three T cell subpopulations and decreases of CCR6 in a NK cell subpopulation were further validated in two independent external cohorts. Moreover, multiple proteins in PBMCs, distinct from the irAE\u2010predicting biomarkers, exhibited differential expression levels corresponding to the differential responses to the PD\u20101 inhibitors. Via multiple independent cohorts, our study revealed crucial roles of CXCR3 and CCR6 in PD\u20101\u2010induced irAEs, provided potential circulating biomarkers associated with toxicity and responses of PD\u20101 inhibitors and further sculptured the landscape of immune cell heterogeneity via focusing on PBMC subpopulations.<\/jats:p>","DOI":"10.1002\/mco2.70721","type":"journal-article","created":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T16:27:08Z","timestamp":1775406428000},"source":"Crossref","is-referenced-by-count":1,"title":["Peripheral Blood Mononuclear Cells Profiling Revealed Biomarkers That Predict PD\u20101 Inhibitor\u2010Induced Immune\u2010Related Adverse Events"],"prefix":"10.1002","volume":"7","author":[{"given":"Jun","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"},{"name":"Shandong Lung Cancer Institute The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"},{"name":"Lung Cancer Center The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"},{"name":"Shandong Lung Cancer Institute The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"},{"name":"Lung Cancer Center The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Gong","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Molecular Imaging Pudong Gongli Hospital Shanghai University of Medicine and Health Sciences  Shanghai China"},{"name":"Shanghai Institute for Advanced Immunochemical Studies ShanghaiTech University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songlin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"},{"name":"Shandong Lung Cancer Institute The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"},{"name":"Lung Cancer Center The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"},{"name":"Shandong Lung Cancer Institute The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"},{"name":"Lung Cancer Center The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuekai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"},{"name":"Shandong Lung Cancer Institute The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"},{"name":"Lung Cancer Center The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"},{"name":"Shandong Lung Cancer Institute The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Department of Thoracic Oncology The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University\/Hunan Cancer Hospital  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology Senior Department of oncology The First Medical Center of Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Pathology Department Renji Hospital of Shanghai Jiaotong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"GMU\u2010GIBH Joint School of Life Sciences The Guangdong\u2010Hong Kong\u2010Macao Joint Laboratory for Cell Fate Regulation and Diseases Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0178-5121","authenticated-orcid":false,"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Molecular Imaging Pudong Gongli Hospital Shanghai University of Medicine and Health Sciences  Shanghai China"},{"name":"Shanghai Institute for Advanced Immunochemical Studies ShanghaiTech University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,5]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1203486"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1992.tb05481.x"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.192461099"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm730"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80089-8"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.291.5502.319"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2024.102536"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08105-5"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02895-x"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06217-y"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-025-01026-w"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02094-6"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-020-0352-8"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02023"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2025-011929"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI176567"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.76"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198704"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-020-00121-4"},{"key":"e_1_2_12_21_1","article-title":"A Mass Cytometry Approach to Track the Evolution of T Cell Responses during Infection and Immunotherapy by Paired T Cell Receptor Repertoire and T Cell Differentiation State Analysis","author":"Castillo J. G.","year":"2024","journal-title":"BioRxiv"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.09.030"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02254-3"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2025.103423"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.29.18288"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.8.2635"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.9.5846"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.23.14893"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.10.1515"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.02.009"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.04.010"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-08-2996"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13783"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI65459"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-22-0112"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.03.039"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2003026117"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16061225"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-025-04287-7"},{"key":"e_1_2_12_40_1","article-title":"Inflammatory Arthritis Immune Related Adverse Events Represent a Unique Autoimmune Disease Entity Primarily Driven by T Cells, but Likely Not Autoantibodies","author":"Zhu X.","year":"2025","journal-title":"medRxiv"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29539-3"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.08.067"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.06.003"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-1868"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2022.04.005"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.062551"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-24-0230"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.03.006"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-025-01001-5"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03699-3"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03398-5"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2022.12.007"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2025-011636"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-025-13566-6"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2025.2668"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2020.7567"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-018-0016-7"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2015.020"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.22271"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29383-5"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3863"},{"key":"e_1_2_12_62_1","first-page":"2579","article-title":"Visualizing Data Using T\u2010SNE","volume":"9","author":"Maaten L.","year":"2008","journal-title":"Journal of Machine Learning Research"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-023-05578-5"}],"container-title":["MedComm"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mco2.70721","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mco2.70721","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mco2.70721","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:57:56Z","timestamp":1776232676000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mco2.70721"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":62,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/mco2.70721"],"URL":"https:\/\/doi.org\/10.1002\/mco2.70721","archive":["Portico"],"relation":{},"ISSN":["2688-2663","2688-2663"],"issn-type":[{"value":"2688-2663","type":"print"},{"value":"2688-2663","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"article-number":"e70721"}}