Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/22602
Title: Stroma remodeling and reduced cell division define durable response to PD-1 blockade in melanoma.
Authors: Galvani, Elena;Mundra, Piyushkumar A;Valpione, Sara;Garcia-Martinez, Pablo;Smith, Matthew;Greenall, Jonathan;Thakur, Rohit;Helmink, Beth;Andrews, Miles C;Boon, Louis;Chester, Christopher;Gremel, Gabriela;Hogan, Kate;Mandal, Amit;Zeng, Kang;Banyard, Antonia;Ashton, Garry;Cook, Martin;Lorigan, Paul;Wargo, Jennifer A;Dhomen, Nathalie;Marais, Richard
Affiliation: Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Manchester, UK
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
The Christie NHS Foundation Trust, Manchester, UK
The University of Manchester, Oxford Road, Manchester, UK
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
La Trobe University School of Cancer Medicine, Heidelberg, VIC, Australia
Bioceros B.V, Utrecht, The Netherlands
Imaging and Cytometry, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Manchester, UK
Histology, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Manchester, UK
Issue Date: 12-Feb-2020
EDate: 2020-02-12
Citation: Nature communications 2020; 11(1): 853
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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/22602
DOI: 10.1038/s41467-020-14632-2
ORCID: 0000-0003-1231-8641
0000-0002-8875-2164
0000-0003-3438-7576
0000-0001-7484-4183
PubMed URL: 32051401
Type: Journal Article
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.