Publications Search

Search for publications by author
Search for publications by abstract keyword(s)

Stromal cell diversity associated with immune evasion in human triple-negative breast cancer


The tumour stroma regulates nearly all stages of carcinogenesis. Stromal heterogeneity in human triple-negative breast cancers (TNBCs) remains poorly understood, limiting the development of stromal-targeted therapies. Single-cell RNA sequencing of five TNBCs revealed two cancer-associated fibroblast (CAF) and two perivascular-like (PVL) subpopulations. CAFs clustered into two states: the first with features of myofibroblasts and the second characterised by high expression of growth factors and immunomodulatory molecules. PVL cells clustered into two states consistent with a differentiated and immature phenotype. We showed that these stromal states have distinct morphologies, spatial relationships and functional properties in regulating the extracellular matrix. Using cell signalling predictions, we provide evidence that stromal-immune crosstalk acts via a diverse array of immunoregulatory molecules. Importantly, the investigation of gene signatures from inflammatory-CAFs and differentiated-PVL cells in independent TNBC patient cohorts revealed strong associations with cytotoxic T-cell dysfunction and exclusion, respectively. Such insights present promising candidates to further investigate for new therapeutic strategies in the treatment of TNBCs.

Type Journal
ISBN 1460-2075 (Electronic) 0261-4189 (Linking)
Authors Wu, S. Z.; Roden, D. L.; Wang, C.; Holliday, H.; Harvey, K.; Cazet, A. S.; Murphy, K. J.; Pereira, B.; Al-Eryani, G.; Bartonicek, N.; Hou, R.; Torpy, J. R.; Junankar, S.; Chan, C. L.; Lam, C. E.; Hui, M. N.; Gluch, L.; Beith, J.; Parker, A.; Robbins, E.; Segara, D.; Mak, C.; Cooper, C.; Warrier, S.; Forrest, A.; Powell, J.; O'Toole, S.; Cox, T. R.; Timpson, P.; Lim, E.; Liu, X. S.; Swarbrick, A.
Responsible Garvan Author Prof Alexander Swarbrick
Publisher Name EMBO JOURNAL
Published Date 2020-10-01
Published Volume 1
Published Issue 39
Published Pages e104063
Status Published in-print
DOI 10.15252/embj.2019104063
URL link to publisher's version