TY - JOUR
T1 - Stroma remodeling and reduced cell division define durable response to PD-1 blockade in melanoma
AU - Galvani, Elena
AU - Mundra, Piyushkumar A.
AU - Valpione, Sara
AU - Garcia-Martinez, Pablo
AU - Smith, Matthew
AU - Greenall, Jonathan
AU - Thakur, Rohit
AU - Helmink, Beth
AU - Andrews, Miles C.
AU - Boon, Louis
AU - Chester, Christopher
AU - Gremel, Gabriela
AU - Hogan, Kate
AU - Mandal, Amit
AU - Zeng, Kang
AU - Banyard, Antonia
AU - Ashton, Garry
AU - Cook, Martin
AU - Lorigan, Paul
AU - Wargo, Jennifer A.
AU - Dhomen, Nathalie
AU - Marais, Richard
PY - 2020/2/12
Y1 - 2020/2/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85079335722&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-14632-2
DO - 10.1038/s41467-020-14632-2
M3 - Article
C2 - 32051401
AN - SCOPUS:85079335722
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 853
ER -