{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T17:07:20Z","timestamp":1793639240336,"version":"4.5.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":36,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82460111"],"award-info":[{"award-number":["82460111"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"DOI":"10.1186\/s12967-026-08004-5","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T16:07:34Z","timestamp":1773763654000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dissecting the immunosuppressive microenvironment of LAMA3\u2009+\u2009malignant cells and SPP1\u2009+\u2009macrophages in esophageal squamous cell carcinoma using single-cell and spatial transcriptomics"],"prefix":"10.1186","volume":"24","author":[{"given":"Kunqiao","family":"Hong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengzhou","family":"Pa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijie","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunrui","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialong","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"8004_CR1","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/s41467-021-21043-4","volume":"12","author":"Y Liu","year":"2021","unstructured":"Liu Y, He S, Wang XL, Peng W, Chen QY, Chi DM, Chen JR, Han BW, Lin GW, Li YQ, et al. Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution. Nat Commun. 2021;12:741.","journal-title":"Nat Commun"},{"key":"8004_CR2","doi-asserted-by":"publisher","first-page":"5029","DOI":"10.1038\/s41467-023-40271-4","volume":"14","author":"R Arora","year":"2023","unstructured":"Arora R, Cao C, Kumar M, Sinha S, Chanda A, McNeil R, Samuel D, Arora RK, Matthews TW, Chandarana S, et al. Spatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response. Nat Commun. 2023;14:5029.","journal-title":"Nat Commun"},{"key":"8004_CR3","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1038\/s41586-019-0969-x","volume":"566","author":"J Cao","year":"2019","unstructured":"Cao J, Spielmann M, Qiu X, Huang X, Ibrahim DM, Hill AJ, Zhang F, Mundlos S, Christiansen L, Steemers FJ, et al. The single-cell transcriptional landscape of mammalian organogenesis. Nature. 2019;566:496\u2013502.","journal-title":"Nature"},{"key":"8004_CR4","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1007\/978-1-0716-0301-7_7","volume":"2117","author":"CB Steen","year":"2020","unstructured":"Steen CB, Liu CL, Alizadeh AA, Newman AM. Profiling Cell Type Abundance and Expression in Bulk Tissues with CIBERSORTx. Methods Mol Biol. 2020;2117:135\u201357.","journal-title":"Methods Mol Biol"},{"key":"8004_CR5","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.jare.2022.10.007","volume":"50","author":"B Zhou","year":"2023","unstructured":"Zhou B, Bie F, Zang R, Zhang M, Song P, Liu L, Peng Y, Bai G, Huai Q, Li Y, et al. Global burden and temporal trends in incidence and mortality of oesophageal cancer. J Adv Res. 2023;50:135\u201344.","journal-title":"J Adv Res"},{"key":"8004_CR6","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209\u201349.","journal-title":"CA Cancer J Clin"},{"key":"8004_CR7","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1053\/j.gastro.2022.05.054","volume":"163","author":"E Morgan","year":"2022","unstructured":"Morgan E, Soerjomataram I, Rumgay H, Coleman HG, Thrift AP, Vignat J, Laversanne M, Ferlay J, Arnold M. The Global Landscape of Esophageal Squamous Cell Carcinoma and Esophageal Adenocarcinoma Incidence and Mortality in 2020 and Projections to 2040: New Estimates From GLOBOCAN 2020. Gastroenterology. 2022;163:649\u2013e658642.","journal-title":"Gastroenterology"},{"key":"8004_CR8","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.canlet.2016.01.043","volume":"387","author":"T Wu","year":"2017","unstructured":"Wu T, Dai Y. Tumor microenvironment and therapeutic response. Cancer Lett. 2017;387:61\u20138.","journal-title":"Cancer Lett"},{"key":"8004_CR9","first-page":"1","volume":"1","author":"The global challenge of cancer","year":"2020","unstructured":"The global challenge of cancer. Nat Cancer. 2020;1:1\u20132.","journal-title":"Nat Cancer"},{"key":"8004_CR10","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.1016\/j.ccell.2023.11.003","volume":"41","author":"J Chang","year":"2023","unstructured":"Chang J, Zhao X, Wang Y, Liu T, Zhong C, Lao Y, Zhang S, Liao H, Bai F, Lin D, Wu C. Genomic alterations driving precancerous to cancerous lesions in esophageal cancer development. Cancer Cell. 2023;41:2038\u201350. e2035.","journal-title":"Cancer Cell"},{"key":"8004_CR11","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1001\/jama.2021.12836","volume":"326","author":"H Luo","year":"2021","unstructured":"Luo H, Lu J, Bai Y, Mao T, Wang J, Fan Q, Zhang Y, Zhao K, Chen Z, Gao S, et al. Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial. JAMA. 2021;326:916\u201325.","journal-title":"JAMA"},{"key":"8004_CR12","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1097\/SLA.0000000000002118","volume":"267","author":"Y Baba","year":"2018","unstructured":"Baba Y, Yoshida N, Kinoshita K, Iwatsuki M, Yamashita YI, Chikamoto A, Watanabe M, Baba H. Clinical and Prognostic Features of Patients With Esophageal Cancer and Multiple Primary Cancers: A Retrospective Single-institution Study. Ann Surg. 2018;267:478\u201383.","journal-title":"Ann Surg"},{"key":"8004_CR13","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1038\/s41392-020-00275-8","volume":"5","author":"HF Hu","year":"2020","unstructured":"Hu HF, Xu WW, Zhang WX, Yan X, Li YJ, Li B, He QY. Identification of miR-515-3p and its targets, vimentin and MMP3, as a key regulatory mechanism in esophageal cancer metastasis: functional and clinical significance. Signal Transduct Target Ther. 2020;5:271.","journal-title":"Signal Transduct Target Ther"},{"key":"8004_CR14","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/s41392-023-01710-2","volume":"8","author":"L Chen","year":"2023","unstructured":"Chen L, Zhu S, Liu T, Zhao X, Xiang T, Hu X, Wu C, Lin D. Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progression. Signal Transduct Target Ther. 2023;8:453.","journal-title":"Signal Transduct Target Ther"},{"key":"8004_CR15","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1016\/j.ccell.2023.03.001","volume":"41","author":"Y Chen","year":"2023","unstructured":"Chen Y, Zhu S, Liu T, Zhang S, Lu J, Fan W, Lin L, Xiang T, Yang J, Zhao X, et al. Epithelial cells activate fibroblasts to promote esophageal cancer development. Cancer Cell. 2023;41:903\u2013e918908.","journal-title":"Cancer Cell"},{"key":"8004_CR16","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.canlet.2018.01.059","volume":"420","author":"H Wu","year":"2018","unstructured":"Wu H, Chen S, Yu J, Li Y, Zhang XY, Yang L, Zhang H, Hou Q, Jiang M, Brunicardi FC, et al. Single-cell Transcriptome Analyses Reveal Molecular Signals to Intrinsic and Acquired Paclitaxel Resistance in Esophageal Squamous Cancer Cells. Cancer Lett. 2018;420:156\u201367.","journal-title":"Cancer Lett"},{"key":"8004_CR17","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1126\/science.1254257","volume":"344","author":"AP Patel","year":"2014","unstructured":"Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H, Cahill DP, Nahed BV, Curry WT, Martuza RL, et al. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 2014;344:1396\u2013401.","journal-title":"Science"},{"key":"8004_CR18","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41592-020-01033-y","volume":"18","author":"V Marx","year":"2021","unstructured":"Marx V. Method of the Year: spatially resolved transcriptomics. Nat Methods. 2021;18:9\u201314.","journal-title":"Nat Methods"},{"key":"8004_CR19","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/nature20123","volume":"539","author":"I Tirosh","year":"2016","unstructured":"Tirosh I, Venteicher AS, Hebert C, Escalante LE, Patel AP, Yizhak K, Fisher JM, Rodman C, Mount C, Filbin MG, et al. Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma. Nature. 2016;539:309\u201313.","journal-title":"Nature"},{"key":"8004_CR20","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","volume":"184","author":"Y Hao","year":"2021","unstructured":"Hao Y, Hao S, Andersen-Nissen E, Mauck WM 3rd, Zheng S, Butler A, Lee MJ, Wilk AJ, Darby C, Zager M, et al. Integrated analysis of multimodal single-cell data. Cell. 2021;184:3573\u2013e35873529.","journal-title":"Cell"},{"key":"8004_CR21","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","volume":"177","author":"T Stuart","year":"2019","unstructured":"Stuart T, Butler A, Hoffman P, Hafemeister C, Papalexi E, Mauck WM 3rd, Hao Y, Stoeckius M, Smibert P, Satija R. Comprehensive Integration of Single-Cell Data. Cell. 2019;177:1888\u2013902. e1821.","journal-title":"Cell"},{"key":"8004_CR22","doi-asserted-by":"publisher","first-page":"15450","DOI":"10.1021\/acs.analchem.3c02029","volume":"95","author":"A Robles-Remacho","year":"2023","unstructured":"Robles-Remacho A, Sanchez-Martin RM, Diaz-Mochon JJ. Spatial Transcriptomics: Emerging Technologies in Tissue Gene Expression Profiling. Anal Chem. 2023;95:15450\u201360.","journal-title":"Anal Chem"},{"key":"8004_CR23","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1038\/s41592-021-01203-6","volume":"18","author":"SM Lewis","year":"2021","unstructured":"Lewis SM, Asselin-Labat M-L, Nguyen Q, Berthelet J, Tan X, Wimmer VC, Merino D, Rogers KL, Naik SH. Spatial omics and multiplexed imaging to explore cancer biology. Nat Methods. 2021;18:997\u20131012.","journal-title":"Nat Methods"},{"key":"8004_CR24","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1016\/j.cell.2020.08.043","volume":"182","author":"AL Ji","year":"2020","unstructured":"Ji AL, Rubin AJ, Thrane K, Jiang S, Reynolds DL, Meyers RM, Guo MG, George BM, Mollbrink A, Bergenstrahle J, et al. Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma. Cell. 2020;182:1661\u20132.","journal-title":"Cell"},{"key":"8004_CR25","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/s41586-021-03634-9","volume":"596","author":"A Rao","year":"2021","unstructured":"Rao A, Barkley D, Fran\u00e7a GS, Yanai I. Exploring tissue architecture using spatial transcriptomics. Nature. 2021;596:211\u201320.","journal-title":"Nature"},{"key":"8004_CR26","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/nature04872","volume":"441","author":"G Christofori","year":"2006","unstructured":"Christofori G. New signals from the invasive front. Nature. 2006;441:444\u201350.","journal-title":"Nature"},{"key":"8004_CR27","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","volume":"16","author":"I Korsunsky","year":"2019","unstructured":"Korsunsky I, Millard N, Fan J, Slowikowski K, Zhang F, Wei K, Baglaenko Y, Brenner M, Loh PR, Raychaudhuri S. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat Methods. 2019;16:1289\u201396.","journal-title":"Nat Methods"},{"key":"8004_CR28","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15\u201321.","journal-title":"Bioinformatics"},{"key":"8004_CR29","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. Omics. 2012;16:284\u20137.","journal-title":"Omics"},{"key":"8004_CR30","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1093\/bioinformatics\/btr260","volume":"27","author":"A Liberzon","year":"2011","unstructured":"Liberzon A, Subramanian A, Pinchback R, Thorvaldsd\u00f3ttir H, Tamayo P, Mesirov JP. Molecular signatures database (MSigDB) 3.0. Bioinformatics. 2011;27:1739\u201340.","journal-title":"Bioinformatics"},{"key":"8004_CR31","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102:15545\u201350.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"8004_CR32","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1471-2105-14-7","volume":"14","author":"S H\u00e4nzelmann","year":"2013","unstructured":"H\u00e4nzelmann S, Castelo R, Guinney J. GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics. 2013;14:7.","journal-title":"BMC Bioinformatics"},{"key":"8004_CR33","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/s41592-019-0667-5","volume":"17","author":"R Browaeys","year":"2020","unstructured":"Browaeys R, Saelens W, Saeys Y. NicheNet: modeling intercellular communication by linking ligands to target genes. Nat Methods. 2020;17:159\u201362.","journal-title":"Nat Methods"},{"key":"8004_CR34","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s13048-021-00807-y","volume":"14","author":"LY Feng","year":"2021","unstructured":"Feng LY, Huang YZ, Zhang W, Li L. LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer. J Ovarian Res. 2021;14:67.","journal-title":"J Ovarian Res"},{"key":"8004_CR35","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1615\/CritRevImmunol.2023051066","volume":"44","author":"B Ning","year":"2024","unstructured":"Ning B, Mei Y. LAMA3 Promotes Tumorigenesis of Oral Squamous Cell Carcinoma by METTL3-Mediated N6-Methyladenosine Modification. Crit Rev Immunol. 2024;44:49\u201359.","journal-title":"Crit Rev Immunol"},{"key":"8004_CR36","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1126\/science.ade2292","volume":"381","author":"R Bill","year":"2023","unstructured":"Bill R, Wirapati P, Messemaker M, Roh W, Zitti B, Duval F, Kiss M, Park JC, Saal TM, Hoelzl J, et al. CXCL9:SPP1 macrophage polarity identifies a network of cellular programs that control human cancers. Science. 2023;381:515\u201324.","journal-title":"Science"},{"key":"8004_CR37","doi-asserted-by":"publisher","first-page":"2143","DOI":"10.1161\/ATVBAHA.123.319828","volume":"43","author":"M Fu","year":"2023","unstructured":"Fu M, Shu S, Peng Z, Liu X, Chen X, Zeng Z, Yang Y, Cui H, Zhao R, Wang X, et al. Single-Cell RNA Sequencing of Coronary Perivascular Adipose Tissue From End-Stage Heart Failure Patients Identifies SPP1(+) Macrophage Subpopulation as a Target for Alleviating Fibrosis. Arterioscler Thromb Vasc Biol. 2023;43:2143\u201364.","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"8004_CR38","doi-asserted-by":"publisher","first-page":"e1115","DOI":"10.1002\/ctm2.1115","volume":"12","author":"J Liu","year":"2022","unstructured":"Liu J, Huang Y, Gong Y, Liu Q, Lin J, Liu J, Liu M, Huang J, Pu W, Ma Y, et al. CTHRC1\u2009+\u2009fibroblasts are stimulated by macrophage-secreted SPP1 to induce excessive collagen deposition in keloids. Clin Transl Med. 2022;12:e1115.","journal-title":"Clin Transl Med"},{"key":"8004_CR39","doi-asserted-by":"publisher","first-page":"1742","DOI":"10.1038\/s41467-022-29366-6","volume":"13","author":"J Qi","year":"2022","unstructured":"Qi J, Sun H, Zhang Y, Wang Z, Xun Z, Li Z, Ding X, Bao R, Hong L, Jia W, et al. Single-cell and spatial analysis reveal interaction of FAP(+) fibroblasts and SPP1(+) macrophages in colorectal cancer. Nat Commun. 2022;13:1742.","journal-title":"Nat Commun"},{"key":"8004_CR40","doi-asserted-by":"crossref","unstructured":"Morse C, Tabib T, Sembrat J, Buschur KL, Bittar HT, Valenzi E, Jiang Y, Kass DJ, Gibson K, Chen W, et al. Proliferating SPP1\/MERTK-expressing macrophages in idiopathic pulmonary fibrosis. Eur Respir J. 2019;54.","DOI":"10.1183\/13993003.02441-2018"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-026-08004-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08004-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08004-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T11:11:33Z","timestamp":1776856293000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12967-026-08004-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,17]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["8004"],"URL":"https:\/\/doi.org\/10.1186\/s12967-026-08004-5","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,17]]},"assertion":[{"value":"30 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"There is no ethical approval applicable, as this study did not involve human participants or animals.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"570"}}