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

2020-02-12

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

Journal Article

0000-0003-1231-8641

0000-0002-8875-2164

0000-0003-3438-7576

0000-0001-7484-4183

10.1038/s41467-020-14632-2

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.

link

Nature Communications 2020; 11(1): 853

Nature Communications