High response rate to PD-1 blockade in desmoplastic melanomas View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-01

AUTHORS

Zeynep Eroglu, Jesse M. Zaretsky, Siwen Hu-Lieskovan, Dae Won Kim, Alain Algazi, Douglas B. Johnson, Elizabeth Liniker, Ben Kong, Rodrigo Munhoz, Suthee Rapisuwon, Pier Federico Gherardini, Bartosz Chmielowski, Xiaoyan Wang, I. Peter Shintaku, Cody Wei, Jeffrey A. Sosman, Richard W. Joseph, Michael A. Postow, Matteo S. Carlino, Wen-Jen Hwu, Richard A. Scolyer, Jane Messina, Alistair J. Cochran, Georgina V. Long, Antoni Ribas

ABSTRACT

Desmoplastic melanoma is a rare subtype of melanoma characterized by dense fibrous stroma, resistance to chemotherapy and a lack of actionable driver mutations, and is highly associated with ultraviolet light-induced DNA damage. We analysed sixty patients with advanced desmoplastic melanoma who had been treated with antibodies to block programmed cell death 1 (PD-1) or PD-1 ligand (PD-L1). Objective tumour responses were observed in forty-two of the sixty patients (70%; 95% confidence interval 57-81%), including nineteen patients (32%) with a complete response. Whole-exome sequencing revealed a high mutational load and frequent NF1 mutations (fourteen out of seventeen cases) in these tumours. Immunohistochemistry analysis from nineteen desmoplastic melanomas and thirteen non-desmoplastic melanomas revealed a higher percentage of PD-L1-positive cells in the tumour parenchyma in desmoplastic melanomas (P = 0.04); these cells were highly associated with increased CD8 density and PD-L1 expression in the tumour invasive margin. Therefore, patients with advanced desmoplastic melanoma derive substantial clinical benefit from PD-1 or PD-L1 immune checkpoint blockade therapy, even though desmoplastic melanoma is defined by its dense desmoplastic fibrous stroma. The benefit is likely to result from the high mutational burden and a frequent pre-existing adaptive immune response limited by PD-L1 expression. More... »

PAGES

347

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature25187

DOI

http://dx.doi.org/10.1038/nature25187

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1100288938

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29320474


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