{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T13:10:45Z","timestamp":1775135445338,"version":"3.50.1"},"reference-count":91,"publisher":"Wiley","issue":"26","license":[{"start":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T00:00:00Z","timestamp":1714348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101830"],"award-info":[{"award-number":["82101830"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202875"],"award-info":[{"award-number":["82202875"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373428"],"award-info":[{"award-number":["82373428"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870425"],"award-info":[{"award-number":["81870425"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82102817"],"award-info":[{"award-number":["82102817"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010248","name":"Zhejiang Province Public Welfare Technology Application Research Project","doi-asserted-by":"publisher","award":["LGF21H030009"],"award-info":[{"award-number":["LGF21H030009"]}],"id":[{"id":"10.13039\/501100010248","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2019YFC0840609"],"award-info":[{"award-number":["2019YFC0840609"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2019YFC0840600"],"award-info":[{"award-number":["2019YFC0840600"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Heterogeneous organ\u2010specific responses to immunotherapy exist in lung cancer. Dissecting tumor microenvironment (TME) can provide new insights into the mechanisms of divergent responses, the process of which remains poor, partly due to the challenges associated with single\u2010cell profiling using formalin\u2010fixed paraffin\u2010embedded (FFPE) materials. In this study, single\u2010cell nuclei RNA sequencing and imaging mass cytometry (IMC) are used to dissect organ\u2010specific cellular and spatial TME based on FFPE samples from paired primary lung adenocarcinoma (LUAD) and metastases. Single\u2010cell analyses of 84 294 cells from sequencing and 250 600 cells from IMC reveal divergent organ\u2010specific immune niches. For sites of LUAD responding well to immunotherapy, including primary LUAD and adrenal gland metastases, a significant enrichment of B, plasma, and T cells is detected. Spatially resolved maps reveal cellular neighborhoods recapitulating functional units of the tumor ecosystem and the spatial proximity of B and CD4<jats:sup>+<\/jats:sup> T cells at immunogenic sites. Various organ\u2010specific densities of tertiary lymphoid structures are observed. Immunosuppressive sites, including brain and liver metastases, are deposited with collagen I, and T cells at these sites highly express TIM\u20103. This study originally deciphers the single\u2010cell landscape of the organ\u2010specific TME at both cellular and spatial levels for LUAD, indicating the necessity for organ\u2010specific treatment approaches.<\/jats:p>","DOI":"10.1002\/advs.202308892","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T05:34:40Z","timestamp":1714368880000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Pathologically Friendly Strategy for Determining the Organ\u2010specific Spatial Tumor Microenvironment Topology in Lung Adenocarcinoma Through the Integration of snRandom\u2010seq and Imaging Mass Cytometry"],"prefix":"10.1002","volume":"11","author":[{"given":"Xuqi","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310003 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310003 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310003 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weihong","family":"Tian","sequence":"additional","affiliation":[{"name":"Changzhou Third People's Hospital Changzhou Medical Center Nanjing Medical University  140 Hanzhong Rd, Gulou Nanjing Jiangsu 210029 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinlin","family":"Cheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310003 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuqiang","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310003 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuzhi","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310003 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Libing","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310003 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongqiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat\u2010sen University Cancer Center  Guangzhou 510060 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomeng","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310003 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linying","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Disease The First Affiliated Hospital College of Medicine Zhejiang University  Hangzhou 310003 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lulu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310003 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310003 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Shi","sequence":"additional","affiliation":[{"name":"Bio\u2010X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders Shanghai Jiao Tong University  1954 Huashan Road Shanghai 200030 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310003 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weijia","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310003 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310003 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6232-3783","authenticated-orcid":false,"given":"Xuanwen","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 310003 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,29]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2014.07.020"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2017.09.151"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01503"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.11058"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-2994"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801005"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32409-7"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30167-6"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-016-0193-2"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-022-02315-2"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000002217"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2020.1823779"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-019-03104-w"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.02.016"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01962-5"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-005320"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-021-03030-8"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2022.10.008"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-021-00292-8"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-023-01164-9"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05672-3"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.10.009"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.12.011"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.32522"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-018-2239-4"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16164-1"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13010185"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38409-5"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05400-x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-21-1101"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.07.013"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-0316"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-021-02731-5"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2013.08.267"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018080810"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11053-8"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abf7777"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0257-x"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.09.031"},{"key":"e_1_2_9_41_1","volume":"132","author":"Wu Z.","year":"2022","journal-title":"J. Clin. Invest."},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200108)31:8<2438::AID-IMMU2438>3.0.CO;2-P"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-0256-z"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00537-8"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1080\/25785826.2019.1698261"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.715234"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.08.017"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1179877"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2018.02.010"},{"key":"e_1_2_9_50_1","volume-title":"Two\u2010dimensional signal and image processing","author":"Lim J. S.","year":"1990"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.5566\/ias.v27.p87-95"},{"key":"e_1_2_9_52_1","first-page":"3989","volume":"2016","author":"Nowak M. R.","year":"2016","journal-title":"Annu. Int. Conf. IEEE Eng. Med. Biol. Soc."},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-01565-y"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-021-00366-w"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-022-01002-x"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0144-6"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.024"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107644"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.2.1081"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.12.5897"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.768"},{"key":"e_1_2_9_62_1","first-page":"3395","volume":"42","author":"Liu Z.","year":"2018","journal-title":"Int J Mol Med"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-14-0275"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1098"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.0980"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.07.017"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-1658"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003534"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2020.10.128"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-021-00151-w"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2022.02.002"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1922-8"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-3876"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan3311"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2019.1659093"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-021-00232-6"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100643"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-015-1752-y"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-0096"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10501"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-000911"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003883"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1382-0"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.73600.1"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39173-2"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.24320"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-023-00881-0"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4391"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202308892","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T12:57:36Z","timestamp":1759755456000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202308892"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,29]]},"references-count":91,"journal-issue":{"issue":"26","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1002\/advs.202308892"],"URL":"https:\/\/doi.org\/10.1002\/advs.202308892","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,29]]},"assertion":[{"value":"2023-11-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2308892"}}