Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma

To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), we combined single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging from a series of human cSCCs and matched normal skin. cSCC exhibited four tumor subpopulations, three recapitulating normal epidermal states, and a tumor-specific keratinocyte (TSK) population unique to cancer, which localized to a fibrovascular niche. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing TSK cells as a hub for intercellular communication. Multiple features of potential immunosuppression were observed, including T regulatory cell (Treg)…

• UD
  U.S. Department of Defense

  Awards: W81XWH-14-1-0180, W81XWH-12-1-0591
• UD
  U.S. Department of Veterans Affairs

  Award: I01BX00140908
• BA
  Bill and Melinda Gates Foundation

  Award: OPP1113682
• CR
  Cancer Research Institute
• LA
  Leukemia and Lymphoma Society

  Award: S10OD018220
• C
  Celgene

  Awards: 134073, 133826
• PI
  Parker Institute for Cancer Immunotherapy
• CR
  Cancer Research UK

  Award: C27165/A29073
• SF
  Stiftelsen för Strategisk Forskning
• C
  Cancerfonden
• V
  Vetenskapsrådet
• NI
  National Institutes of Health

  Awards: 5U19AI100627-07, AR43799, 2U19AI057229-16, CA142635, 5F99CA212231-02, 5R33CA18365403, R01HL128173-04, 5P01HL10879707, 5U54CA20997103, IDIQ17X149, 1F32CA233203-01, 1U19AI135976-01, 5U01AI140498-02, R33CA183692, 5R01CA19665703, 5R01GM10983604, 1U54HG010426-01, 5UH2AR06767604, 1U2CCA233195-01, 5U01AI101984-07, T32AR007422, 5P01AI131374-02, 1R01HL120724-01A1, 5UG3DK114937-02, S10OD018220, 1U2CCA233238-01
• UF
  U.S. Food and Drug Administration

  Awards: DSTL/AGR00980, HHSF223201610018C