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Stroma remodeling and reduced cell division define durable response to PD-1 blockade in melanoma
Galvani, Elena Mundra, Piyushkumar A Valpione, Sara Garcia-Martinez, Pablo Smith, Matthew Greenall, Jonathan Thakur, R Helmink, B Andrews, MC Boon, L
Galvani, Elena
Mundra, Piyushkumar A
Valpione, Sara
Garcia-Martinez, Pablo
Smith, Matthew
Greenall, Jonathan
Thakur, R
Helmink, B
Andrews, MC
Boon, L
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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.
Authors
Galvani, Elena
Mundra, Piyushkumar A
Valpione, Sara
Garcia-Martinez, Pablo
Smith, Matthew
Greenall, Jonathan
Thakur, R
Helmink, B
Andrews, MC
Boon, L
Chester, Christopher P E
Gremel, Gabriela
Hogan, Kate
Mandal, Amit Kumar
Zeng, Kang
Banyard, Antonia
Ashton, Garry
Cook, Martin G
Lorigan, Paul C
Wargo, JA
Dhomen, Nathalie
Marais, Richard
Mundra, Piyushkumar A
Valpione, Sara
Garcia-Martinez, Pablo
Smith, Matthew
Greenall, Jonathan
Thakur, R
Helmink, B
Andrews, MC
Boon, L
Chester, Christopher P E
Gremel, Gabriela
Hogan, Kate
Mandal, Amit Kumar
Zeng, Kang
Banyard, Antonia
Ashton, Garry
Cook, Martin G
Lorigan, Paul C
Wargo, JA
Dhomen, Nathalie
Marais, Richard
Description
Date
2020
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Article
Citation
Galvani E, Mundra PA, Valpione S, Garcia-Martinez P, Smith M, Greenall J, et al. Stroma remodeling and reduced cell division define durable response to PD-1 blockade in melanoma. Nat Commun. 2020;11:853.