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

Autor:	Wu SZ; The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia., Roden DL; The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia., Wang C; Department of Data Sciences, Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Holliday H; The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia., Harvey K; The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia., Cazet AS; The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia., Murphy KJ; The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia., Pereira B; The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia., Al-Eryani G; The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia., Bartonicek N; The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia., Hou R; Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, Perth, WA, Australia., Torpy JR; The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia., Junankar S; The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia., Chan CL; Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, NSW, Australia., Lam CE; Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, NSW, Australia., Hui MN; The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; Chris O'Brien Lifehouse, Camperdown, NSW, Australia., Gluch L; The Strathfield Breast Centre, Strathfield, NSW, Australia., Beith J; Chris O'Brien Lifehouse, Camperdown, NSW, Australia., Parker A; St Vincent's Hospital, Darlinghurst, NSW, Australia., Robbins E; Royal Prince Alfred Hospital, Camperdown, NSW, Australia., Segara D; St Vincent's Hospital, Darlinghurst, NSW, Australia., Mak C; Chris O'Brien Lifehouse, Camperdown, NSW, Australia., Cooper C; Pathology Queensland, Princess Alexandra Hospital, Brisbane, Qld, Australia.; Southside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, Qld, Australia., Warrier S; Department of Breast Surgery, Chris O'Brien Lifehouse, Camperdown, NSW, Australia.; Royal Prince Alfred Institute of Academic Surgery, Sydney University, Sydney, NSW, Australia., Forrest A; Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, Perth, WA, Australia.; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Powell J; Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, NSW, Australia.; UNSW Cellular Genomics Futures Institute, University of New South Wales, Sydney, NSW, Australia., O'Toole S; The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia.; Australian Clinical Laboratories, Northern Beaches Hospital, Frenchs Forest, NSW, Australia., Cox TR; The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia., Timpson P; The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia., Lim E; The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia.; St Vincent's Hospital, Darlinghurst, NSW, Australia., Liu XS; Department of Data Sciences, Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Swarbrick A; The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia.
Jazyk:	angličtina
Zdroj:	The EMBO journal [EMBO J] 2020 Oct 01; Vol. 39 (19), pp. e104063. Date of Electronic Publication: 2020 Aug 13.
DOI:	10.15252/embj.2019104063
Abstrakt:	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. (© 2020 The Authors.)
Databáze:	MEDLINE
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