{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T20:34:45Z","timestamp":1777062885991,"version":"3.51.4"},"posted":{"date-parts":[[2025,3,19]]},"group-title":"Immunology","reference-count":61,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Adult-onset dermatomyositis (DM) is an autoimmune inflammatory myopathy with distinct cutaneous manifestations and a strong malignancy association. Through comparative analysis with cutaneous lupus erythematosus (CLE), our integrated spatial and single-cell transcriptomics analysis revealed unique immune and stromal niches associated with DM subtypes. Unexpectedly, we found an association between cancer-associated DM skin lesions and the presence of dispersed immune infiltrates enriched with macrophages, CD8+ T cells, plasma cells, and B cells with preserved vascular architecture. In contrast, non-cancer associated DM skin exhibited dense myeloid cell infiltrates, including neutrophils, monocytes, and macrophages, with elevated expression of IL1B and CXCL10 localized near injured vascular endothelia. Cytokines produced by these myeloid infiltrates together with local tissue hypoxia triggered dramatic stromal remodeling, leading to loss of vascular-associated fibroblasts. In addition to the CXCL10+ myeloid signature, non-cancer-associated DM skin with pDC presence showed the emergence of specific cellular pairs: PD-L1-expressing mregDCs and activated Tregs expressing NFKB2 and TNF receptors. While both DM and CLE showed strong interferon signatures, DM uniquely displayed IFN-\u03b2 expression. Together, our study provides the first comprehensive spatial mapping of immune and stromal cells in adult-onset DM.<\/jats:p>","DOI":"10.1101\/2025.03.19.644147","type":"posted-content","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T19:04:59Z","timestamp":1742583899000},"source":"Crossref","is-referenced-by-count":1,"title":["Spatial Transcriptomics Identifies Immune-Stromal Niches Associated with Cancer in Adult Dermatomyositis"],"prefix":"10.64898","author":[{"given":"Ksenia S.","family":"Anufrieva","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Inflammation, and Immunity, Brigham and Women\u2019s Hospital at Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neda","family":"Shahriari","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ce","family":"Gao","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation, and Immunity, Brigham and Women\u2019s Hospital at Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rochelle L.","family":"Castillo","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation, and Immunity, Brigham and Women\u2019s Hospital at Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean","family":"Prell","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation, and Immunity, Brigham and Women\u2019s Hospital at Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shideh","family":"Kazerounian","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation, and Immunity, Brigham and Women\u2019s Hospital at Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khashayar","family":"Afshari","sequence":"additional","affiliation":[{"name":"Department of Dermatology, UMass Chan Medical School, Worcester, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasia N.","family":"Kazakova","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin","family":"Theisen","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation, and Immunity, Brigham and Women\u2019s Hospital at Harvard Medical School, Boston, MA, USA"},{"name":"Department of Dermatology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Bowman","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avery","family":"LaChance","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly","family":"Hashemi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilya","family":"Korsunsky","sequence":"additional","affiliation":[{"name":"Division of Genetics, Brigham and Women\u2019s Hospital at Harvard Medical School, Boston, MA, USA"},{"name":"Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA"},{"name":"Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehdi","family":"Rashighi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, UMass Chan Medical School, Worcester, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth Ann","family":"Vleugels","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Wei","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation, and Immunity, Brigham and Women\u2019s Hospital at Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041123430674000_2025.03.19.644147v1.1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/s41572-021-00321-x","article-title":"Idiopathic inflammatory myopathies","volume":"7","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"2026041123430674000_2025.03.19.644147v1.2","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s12016-017-8652-1","article-title":"Cutaneous Manifestations of Dermatomyositis: a Comprehensive Review","volume":"53","year":"2017","journal-title":"Clin Rev Allergy Immunol"},{"key":"2026041123430674000_2025.03.19.644147v1.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199202063260602"},{"key":"2026041123430674000_2025.03.19.644147v1.4","first-page":"1300","article-title":"Elevated cancer incidence in patients with dermatomyositis: a population based study","volume":"22","year":"1995","journal-title":"J Rheumatol"},{"key":"2026041123430674000_2025.03.19.644147v1.5","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1177\/1203475416665601","article-title":"Risk of Malignancy in Dermatomyositis and Polymyositis","volume":"21","year":"2017","journal-title":"J Cutan Med Surg"},{"key":"2026041123430674000_2025.03.19.644147v1.6","first-page":"409","article-title":"Dermatomyositis and malignancy","volume":"65","year":"2019","journal-title":"Canadian Family Physician"},{"key":"2026041123430674000_2025.03.19.644147v1.7","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kew215"},{"key":"2026041123430674000_2025.03.19.644147v1.8","first-page":"990","article-title":"Strong correlation between cancer progression and anti-transcription intermediary factor 1\u03b3 antibodies in dermatomyositis patients","volume":"36","year":"2018","journal-title":"Clin Exp Rheumatol"},{"key":"2026041123430674000_2025.03.19.644147v1.9","doi-asserted-by":"crossref","first-page":"992","DOI":"10.3389\/fimmu.2017.00992","article-title":"Dermatomyositis and Immune-Mediated Necrotizing Myopathies: A Window on Autoimmunity and Cancer","volume":"8","year":"2017","journal-title":"Front Immunol"},{"key":"2026041123430674000_2025.03.19.644147v1.10","doi-asserted-by":"publisher","DOI":"10.1101\/2021.11.03.467020"},{"key":"2026041123430674000_2025.03.19.644147v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.03.041"},{"key":"2026041123430674000_2025.03.19.644147v1.12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2203828120"},{"key":"2026041123430674000_2025.03.19.644147v1.13","doi-asserted-by":"publisher","DOI":"10.1101\/2024.03.26.586902"},{"key":"2026041123430674000_2025.03.19.644147v1.14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0560.2009.01443.x"},{"key":"2026041123430674000_2025.03.19.644147v1.15","doi-asserted-by":"crossref","unstructured":"Ramirez Flores, R. O. , Lanzer, J. D. , Dimitrov, D. , Velten, B. & Saez-Rodriguez, J. Multicellular factor analysis of single-cell data for a tissue-centric understanding of disease. Elife 12, (2023).","DOI":"10.7554\/eLife.93161"},{"key":"2026041123430674000_2025.03.19.644147v1.16","doi-asserted-by":"crossref","first-page":"1163633","DOI":"10.3389\/fimmu.2023.1163633","article-title":"The role of PD-1 signaling in health and immune-related diseases","volume":"14","year":"2023","journal-title":"Front. Immunol"},{"key":"2026041123430674000_2025.03.19.644147v1.17","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.15006"},{"key":"2026041123430674000_2025.03.19.644147v1.18","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0140-6736(24)02071-3","article-title":"Efficacy, safety, and target engagement of dazukibart, an IFN\u03b2 specific monoclonal antibody, in adults with dermatomyositis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial","volume":"405","year":"2025","journal-title":"Lancet"},{"key":"2026041123430674000_2025.03.19.644147v1.19","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061825"},{"key":"2026041123430674000_2025.03.19.644147v1.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04642-z"},{"key":"2026041123430674000_2025.03.19.644147v1.21","doi-asserted-by":"crossref","unstructured":"Zhang, N. , Lei, T. , Xu, T. , Zou, X. & Wang, Z . Long noncoding RNA SNHG15: A promising target in human cancers. Frontiers in Oncology 13, 1108564 (2023).","DOI":"10.3389\/fonc.2023.1108564"},{"key":"2026041123430674000_2025.03.19.644147v1.22","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1186\/s12885-020-07649-9","article-title":"Long non-coding RNA SNHG15 in various cancers: a meta and bioinformatic analysis","volume":"20","year":"2020","journal-title":"BMC Cancer"},{"key":"2026041123430674000_2025.03.19.644147v1.23","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww122"},{"key":"2026041123430674000_2025.03.19.644147v1.24","doi-asserted-by":"crossref","unstructured":"Dunlap, G. S. , et al. Single-cell transcriptomics reveals distinct effector profiles of infiltrating T cells in lupus skin and kidney. JCI Insight 7, (2022).","DOI":"10.1172\/jci.insight.156341"},{"key":"2026041123430674000_2025.03.19.644147v1.25","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abn2263"},{"key":"2026041123430674000_2025.03.19.644147v1.26","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.139949"},{"key":"2026041123430674000_2025.03.19.644147v1.27","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-3582695\/v1"},{"key":"2026041123430674000_2025.03.19.644147v1.28","doi-asserted-by":"publisher","DOI":"10.1002\/art.38298"},{"key":"2026041123430674000_2025.03.19.644147v1.29","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1097\/CM9.0000000000002788","article-title":"Vasculopathy in dermatomyositis","volume":"137","year":"2024","journal-title":"Chin Med J (Engl)"},{"key":"2026041123430674000_2025.03.19.644147v1.30","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s10067-017-3799-y","article-title":"Neutrophil extracellular traps may contribute to interstitial lung disease associated with anti-MDA5 autoantibody positive dermatomyositis","volume":"37","year":"2018","journal-title":"Clin Rheumatol"},{"key":"2026041123430674000_2025.03.19.644147v1.31","doi-asserted-by":"crossref","unstructured":"Seto, N. , et al. Neutrophil dysregulation is pathogenic in idiopathic inflammatory myopathies. JCI Insight 5, (2020).","DOI":"10.1172\/jci.insight.134189"},{"key":"2026041123430674000_2025.03.19.644147v1.32","doi-asserted-by":"crossref","unstructured":"Li, T. M. et al. The interferon-rich skin environment regulates Langerhans cell ADAM17 to promote photosensitivity in lupus. Elife 13, (2024).","DOI":"10.7554\/eLife.85914"},{"key":"2026041123430674000_2025.03.19.644147v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.08.032"},{"key":"2026041123430674000_2025.03.19.644147v1.34","doi-asserted-by":"publisher","DOI":"10.1007\/BF00051675"},{"key":"2026041123430674000_2025.03.19.644147v1.35","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-023-01045-w"},{"key":"2026041123430674000_2025.03.19.644147v1.36","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1007\/s12016-022-08944-y","article-title":"Autoantibodies and Cancer Association: the Case of Systemic Sclerosis and Dermatomyositis","volume":"63","year":"2022","journal-title":"Clin Rev Allergy Immunol"},{"key":"2026041123430674000_2025.03.19.644147v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0144-6"},{"key":"2026041123430674000_2025.03.19.644147v1.38","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/art.33402","article-title":"Autoantibodies to transcription intermediary factor 1 in dermatomyositis shed insight into the cancer-myositis connection","volume":"64","year":"2012","journal-title":"Arthritis Rheum"},{"key":"2026041123430674000_2025.03.19.644147v1.39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094128"},{"key":"2026041123430674000_2025.03.19.644147v1.40","doi-asserted-by":"crossref","unstructured":"Fiorentino, D. F. et al. Immune responses to CCAR1 and other dermatomyositis autoantigens are associated with attenuated cancer emergence. J Clin Invest 132, (2022).","DOI":"10.1172\/JCI150201"},{"key":"2026041123430674000_2025.03.19.644147v1.41","doi-asserted-by":"crossref","unstructured":"Strauss, L. et al. Targeted deletion of PD-1 in myeloid cells induces antitumor immunity. Sci Immunol 5, (2020).","DOI":"10.1126\/sciimmunol.aay1863"},{"key":"2026041123430674000_2025.03.19.644147v1.42","doi-asserted-by":"publisher","DOI":"10.1038\/nature22396"},{"key":"2026041123430674000_2025.03.19.644147v1.43","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01170-w"},{"key":"2026041123430674000_2025.03.19.644147v1.44","doi-asserted-by":"crossref","unstructured":"You, S. et al. Lymphatic-localized Treg-mregDC crosstalk limits antigen trafficking and restrains anti-tumor immunity. Cancer cell 42, (2024).","DOI":"10.1016\/j.ccell.2024.06.014"},{"key":"2026041123430674000_2025.03.19.644147v1.45","doi-asserted-by":"crossref","first-page":"114819","DOI":"10.1016\/j.celrep.2024.114819","article-title":"PD-L1 restrains PD-1Nrp1 Treg cells to suppress inflammation-driven colorectal tumorigenesis","volume":"43","year":"2024","journal-title":"Cell Rep"},{"key":"2026041123430674000_2025.03.19.644147v1.46","doi-asserted-by":"publisher","DOI":"10.1038\/S41587-023-01767-Y"},{"key":"2026041123430674000_2025.03.19.644147v1.47","doi-asserted-by":"crossref","first-page":"979","DOI":"10.12688\/f1000research.73600.1","article-title":"Doublet identification in single-cell sequencing data using","volume":"10","year":"2021","journal-title":"F1000Res"},{"key":"2026041123430674000_2025.03.19.644147v1.48","doi-asserted-by":"crossref","unstructured":"Young, M. D. & Behjati, S . SoupX removes ambient RNA contamination from droplet-based single-cell RNA sequencing data. Gigascience 9, (2020).","DOI":"10.1093\/gigascience\/giaa151"},{"key":"2026041123430674000_2025.03.19.644147v1.49","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0"},{"key":"2026041123430674000_2025.03.19.644147v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2023.03.1679"},{"key":"2026041123430674000_2025.03.19.644147v1.51","doi-asserted-by":"publisher","DOI":"10.1101\/2023.10.29.563503"},{"key":"2026041123430674000_2025.03.19.644147v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2016.08.010"},{"key":"2026041123430674000_2025.03.19.644147v1.53","doi-asserted-by":"publisher","DOI":"10.1101\/653253"},{"key":"2026041123430674000_2025.03.19.644147v1.54","doi-asserted-by":"crossref","unstructured":"Chen, Y. , Chen, L. , Lun, A. T. L. , Baldoni, P. L. & Smyth, G. K . edgeR v4: powerful differential analysis of sequencing data with expanded functionality and improved support for small counts and larger datasets. Nucleic Acids Res 53, (2025).","DOI":"10.1093\/nar\/gkaf018"},{"key":"2026041123430674000_2025.03.19.644147v1.55","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2026041123430674000_2025.03.19.644147v1.56","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37822-0"},{"key":"2026041123430674000_2025.03.19.644147v1.57","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0572-2"},{"key":"2026041123430674000_2025.03.19.644147v1.58","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/s41467-024-55700-1","article-title":"Characterizing cell-type spatial relationships across length scales in spatially resolved omics data","volume":"16","year":"2025","journal-title":"Nat Commun"},{"key":"2026041123430674000_2025.03.19.644147v1.59","doi-asserted-by":"publisher","DOI":"10.1101\/2023.09.19.558514"},{"key":"2026041123430674000_2025.03.19.644147v1.60","doi-asserted-by":"crossref","first-page":"vbac016","DOI":"10.1093\/bioadv\/vbac016","article-title":"decoupleR: ensemble of computational methods to infer biological activities from omics data","volume":"2","year":"2022","journal-title":"Bioinform Adv"},{"key":"2026041123430674000_2025.03.19.644147v1.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2021.06.043"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.03.19.644147","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T06:43:16Z","timestamp":1775976196000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.03.19.644147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,19]]},"references-count":61,"URL":"https:\/\/doi.org\/10.1101\/2025.03.19.644147","relation":{},"subject":[],"published":{"date-parts":[[2025,3,19]]},"subtype":"preprint"}}