Spatial Transcriptomics Identifies Immune-Stromal Niches Associated with Cancer in Adult Dermatomyositis

Ksenia S. Anufrieva, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital at Harvard Medical School, Boston, MA, USA.
Neda Shahriari, Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Ce Gao, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital at Harvard Medical School, Boston, MA, USA.
Rochelle L. Castillo, Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jessica Liu, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital at Harvard Medical School, Boston, MA, USA.
Sean Prell, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital at Harvard Medical School, Boston, MA, USA.
Shideh Kazerounian, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital at Harvard Medical School, Boston, MA, USA.
Khashayar Afshari, Department of Dermatology, UMass Chan Medical School, Worcester, MA, USA.
Anastasia N. Kazakova, Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia.
Erin Theisen, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital at Harvard Medical School, Boston, MA, USA.
Teresa Bowman, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Avery LaChance, Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Kimberly Hashemi, Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Ilya Korsunsky, Division of Genetics, Brigham and Women's Hospital at Harvard Medical School, Boston, MA, USA.
Mehdi Rashighi, Department of Dermatology, UMass Chan Medical School, Worcester, MA, USA.
Ruth Ann Vleugels, Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Kevin Wei, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital at Harvard Medical School, Boston, MA, USA.

Document Type

Article

Publication Title

bioRxiv : the preprint server for biology

Abstract

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-β expression. Together, our study provides the first comprehensive spatial mapping of immune and stromal cells in adult-onset DM.

DOI

10.1101/2025.03.19.644147

Publication Date

3-19-2025

Identifier

40166232 (pubmed); PMC11957040 (pmc); 10.1101/2025.03.19.644147 (doi); 2025.03.19.644147 (pii)

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