TGF-β-associated extracellular matrix genes link cancer-associated fibroblasts to immune evasion and immunotherapy failure

Ankur Chakravarthy, Lubaba Khan, Nathan Peter Bensler, Pinaki Bose () and Daniel D. De Carvalho ()
Additional contact information
Ankur Chakravarthy: University Health Network
Lubaba Khan: University of Calgary
Nathan Peter Bensler: University of Calgary
Pinaki Bose: University of Calgary
Daniel D. De Carvalho: University Health Network

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract The extracellular matrix (ECM) is a key determinant of cancer progression and prognosis. Here we report findings from one of the largest pan-cancer analyses of ECM gene dysregulation in cancer. We define a distinct set of ECM genes upregulated in cancer (C-ECM) and linked to worse prognosis. We found that the C-ECM transcriptional programme dysregulation is correlated with the activation of TGF-β signalling in cancer-associated fibroblasts and is linked to immunosuppression in otherwise immunologically active tumours. Cancers that activate this programme carry distinct genomic profiles, such as BRAF, SMAD4 and TP53 mutations and MYC amplification. Finally, we show that this signature is a predictor of the failure of PD-1 blockade and outperforms previously-proposed biomarkers. Thus, our findings identify a distinct transcriptional pattern of ECM genes in operation across cancers that may be potentially targeted, pending preclinical validation, using TGF-β blockade to enhance responses to immune-checkpoint blockade.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-06654-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06654-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-06654-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().