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

Lookup NU author(s): Professor Muzlifah Haniffa



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2020 The AuthorsHere, 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.© 2020 The AuthorsDavidson et al. use scRNA-seq to demonstrate the increasing heterogeneity within the stroma as a tumor develops. They show that T cell activation occurs at the tumor following recruitment from lymph nodes and reveal the presence of three dynamic stromal populations that display unique functional properties.

Publication metadata

Author(s): Davidson S, Efremova M, Riedel A, Mahata B, Pramanik J, Huuhtanen J, Kar G, Vento-Tormo R, Hagai T, Chen X, Haniffa MA, Shields JD, Teichmann SA

Publication type: Article

Publication status: Published

Journal: Cell Reports

Year: 2020

Volume: 31

Issue: 7

Online publication date: 19/05/2020

Acceptance date: 18/04/2020

Date deposited: 29/05/2020

ISSN (print): 2211-1247

ISSN (electronic): 2211-1247

Publisher: Elsevier B.V.


DOI: 10.1016/j.celrep.2020.107628


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