Tumour-intrinsic endomembrane trafficking by ARF6 shapes an immunosuppressive microenvironment that drives melanomagenesis and response to checkpoint blockade therapy

Yinshen Wee, Junhua Wang, Emily C. Wilson, Coulson P. Rich, Aaron Rogers, Zongzhong Tong, Evelyn DeGroot, Y. N. Vashisht Gopal, Michael A. Davies, H. Atakan Ekiz, Joshua K. H. Tay, Chris Stubben, Kenneth M. Boucher, Juan M. Oviedo, Keke C. Fairfax, Matthew A. Williams, Sheri L. Holmen, Roger K. Wolff and Allie H. Grossmann ()
Additional contact information
Yinshen Wee: University of Utah
Junhua Wang: Huntsman Cancer Institute
Emily C. Wilson: University of Utah
Coulson P. Rich: University of Utah
Aaron Rogers: University of Utah
Zongzhong Tong: University of Utah
Evelyn DeGroot: The University of Texas MD Anderson Cancer Center
Y. N. Vashisht Gopal: The University of Texas MD Anderson Cancer Center
Michael A. Davies: The University of Texas MD Anderson Cancer Center
H. Atakan Ekiz: Urla
Joshua K. H. Tay: University of Utah
Chris Stubben: Huntsman Cancer Institute
Kenneth M. Boucher: Huntsman Cancer Institute
Juan M. Oviedo: University of Utah
Keke C. Fairfax: University of Utah
Matthew A. Williams: University of Utah
Sheri L. Holmen: Huntsman Cancer Institute
Roger K. Wolff: University of Utah
Allie H. Grossmann: University of Utah

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Tumour-host immune interactions lead to complex changes in the tumour microenvironment (TME), impacting progression, metastasis and response to therapy. While it is clear that cancer cells can have the capacity to alter immune landscapes, our understanding of this process is incomplete. Herein we show that endocytic trafficking at the plasma membrane, mediated by the small GTPase ARF6, enables melanoma cells to impose an immunosuppressive TME that accelerates tumour development. This ARF6-dependent TME is vulnerable to immune checkpoint blockade therapy (ICB) but in murine melanoma, loss of Arf6 causes resistance to ICB. Likewise, downregulation of ARF6 in patient tumours correlates with inferior overall survival after ICB. Mechanistically, these phenotypes are at least partially explained by ARF6-dependent recycling, which controls plasma membrane density of the interferon-gamma receptor. Collectively, our findings reveal the importance of endomembrane trafficking in outfitting tumour cells with the ability to shape their immune microenvironment and respond to immunotherapy.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-50881-1 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:15:y:2024:i:1:d:10.1038_s41467-024-50881-1

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

DOI: 10.1038/s41467-024-50881-1

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 ().