Journal
CELL REPORTS
Volume 31, Issue 7, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.107628
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Funding
- Cancer Research UK Cancer Immunology Fund [20193]
- European Research Council [260507, 646794]
- European Union Future and Emerging Technologies (FET)-Open grant (MRG-GRAMMAR) [664918]
- Wellcome Sanger core funding [WT206194]
- Medical Research Council [MC_UU_12022/5]
- MRC [MC_UU_12022/5] Funding Source: UKRI
- European Research Council (ERC) [646794] Funding Source: European Research Council (ERC)
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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.
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