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. WargoNathalie Dhomen, Richard Marais

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2 Citations (Scopus)

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.

Original languageEnglish
Article number853
Number of pages9
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 12 Feb 2020
Externally publishedYes

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