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

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Davidson, Sarah 
Efremova, Mirjana 
Riedel, Angela 
Pramanik, Jhuma 

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 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.

cancer-associated fibroblast, cell-cell communication, immune, melanoma, single-cell sequencing, stroma, tumour microenvironment, Animals, Humans, Melanoma, Mice, Sequence Analysis, RNA, Stromal Cells, Tumor Microenvironment
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Elsevier BV
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Medical Research Council (MC_UU_12022/5)
CRUK Cancer Immunology fund (Ref. 20193) Joint J Shields and Sarah Teichmann, Medical Research Council core funding - J Shields ERC grants (ThSWITCH, grant number 260507; ThDEFINE, Project ID 646794), an EU FET-OPEN grant (MRG-GRAMMAR No 664918), Wellcome Sanger core funding (No WT206194) - Sarah Teichmann