Stroma remodeling and reduced cell division define durable response to PD-1 blockade in melanoma

Elena Galvani, Piyushkumar A. Mundra, Sara Valpione, Pablo Garcia-Martinez, Matthew Smith, Jonathan Greenall, Rohit Thakur, Beth Helmink, Miles C. Andrews, Louis Boon, Christopher Chester, Gabriela Gremel, Kate Hogan, Amit Mandal, Kang Zeng, Antonia Banyard, Garry Ashton, Martin Cook, Paul Lorigan, Jennifer A. Wargo, Nathalie Dhomen and Richard Marais ()
Additional contact information
Elena Galvani: The University of Manchester
Piyushkumar A. Mundra: The University of Manchester
Sara Valpione: The University of Manchester
Pablo Garcia-Martinez: The University of Manchester
Matthew Smith: The University of Manchester
Jonathan Greenall: The University of Manchester
Rohit Thakur: The University of Texas MD Anderson Cancer Center
Beth Helmink: The University of Texas MD Anderson Cancer Center
Miles C. Andrews: The University of Texas MD Anderson Cancer Center
Louis Boon: Bioceros B.V
Christopher Chester: The University of Manchester
Gabriela Gremel: The University of Manchester
Kate Hogan: The University of Manchester
Amit Mandal: The University of Manchester
Kang Zeng: The University of Manchester
Antonia Banyard: The University of Manchester
Garry Ashton: The University of Manchester
Martin Cook: The University of Manchester
Paul Lorigan: The Christie NHS Foundation Trust
Jennifer A. Wargo: The University of Texas MD Anderson Cancer Center
Nathalie Dhomen: The University of Manchester
Richard Marais: The University of Manchester

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: Abstract Although immune checkpoint inhibitors (ICIs) have achieved unprecedented results in melanoma, the biological features of the durable responses initiated by these drugs remain unknown. Here we show the genetic and phenotypic changes induced by treatment with programmed cell death-1 (PD-1) blockade in a genetically engineered mouse model of melanoma driven by oncogenic BRAF. In this controlled system anti-PD-1 treatment yields responses in ~35% of the tumors, and prolongs survival in ~27% of the animals. We identify increased stroma remodeling and reduced expression of proliferation markers as features associated with prolonged response. These traits are corroborated in two independent early on-treatment anti-PD-1 melanoma patient cohorts. These insights into the biological responses of tumors to ICI provide a strategy for identification of durable response early during the course of treatment and could improve patient stratification for checkpoint inhibitory drugs.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-14632-2 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:11:y:2020:i:1:d:10.1038_s41467-020-14632-2

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

DOI: 10.1038/s41467-020-14632-2

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 ().