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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 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.© 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.
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
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.
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