Single-Cell RNA Sequencing Reveals a Dynamic Stromal Niche That Supports Tumor Growth

Sarah Davidson, Mirjana Efremova, Angela Riedel, Bidesh Mahata, Jhuma Pramanik, Jani Huuhtanen, Gozde Kar, Roser Vento-Tormo, Tzachi Hagai, Xi Chen, Muzlifah A. Haniffa, Jacqueline D. Shields, Sarah A. Teichmann

Research output: Contribution to journalArticlepeer-review

Abstract

Here, using single-cell RNA sequencing, we examine the stromal compartment in murine melanoma and draining lymph nodes (LNs) at points across tumor development, providing data at http://www.teichlab.org/data/. Naive lymphocytes from LNs undergo activation and clonal expansion within the tumor, before PD1 and Lag3 expression, while tumor-associated myeloid cells promote the formation of a suppressive niche. We identify three temporally distinct stromal populations displaying unique functional signatures, conserved across mouse and human tumors. Whereas “immune” stromal cells are observed in early tumors, “contractile” cells become more prevalent at later time points. Complement component C3 is specifically expressed in the immune population. Its cleavage product C3a supports the recruitment of C3aR+ macrophages, and perturbation of C3a and C3aR disrupts immune infiltration, slowing tumor growth. Our results highlight the power of scRNA-seq to identify complex interplays and increase stromal diversity as a tumor develops, revealing that stromal cells acquire the capacity to modulate immune landscapes from early disease.

Original languageEnglish
Article number107628
JournalCell Reports
Volume31
Issue number7
DOIs
StatePublished - 19 May 2020

Keywords

  • cancer-associated fibroblast
  • cell-cell communication
  • immune
  • melanoma
  • single-cell sequencing
  • stroma
  • tumour microenvironment

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology

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