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High response rate to anti PD-1 therapy in desmoplastic melanoma

UID: 10710

Author(s): Ribas, Antoni

Description
Study Description from dbGaP: Desmoplastic melanoma (DM) is a rare subtype of melanoma characterized by dense fibrous stroma, resistance to chemotherapy and a lack of actionable driver mutations, but is highly associated with ultraviolet light DNA damage. We analysed 60 patients with advanced DM treated with programmed cell death 1 (PD-1) or PD-1 ligand (PD-L1) blocking antibody therapy. Objective tumor responses were observed in 42 of the 60 patients (70%, 95% confidence interval 57-81%), including 19 patients (32% overall) with a complete response. Whole-exome sequencing revealed a high mutational load and frequent NF-1 mutations (14 out of 17 cases). Immunohistochemistry (IHC) analysis from 19 DM and 13 non-DM revealed a higher percentage of PD-L1 positive cells in the tumor parenchyma in DM (p = 0.04), highly associated with increased CD8 density and PD-L1 expression in the tumor invasive margin. Therefore, patients with advanced DM derive significant clinical benefit from PD-1/PD-L1 immune checkpoint blockade therapy despite being a cancer defined by its dense desmoplastic fibrous stroma. The benefit is likely derived from the high mutational burden and a frequent pre-existing adaptive immune response limited by PD-L1 expression."
Subject of Study
Subject(s)
OncoTree Cancer Type(s)
Desmoplastic Melanoma
Access via dbGaP

FASTQ and SRA files of whole exome sequencing runs.
Accession #: phs001469.v1.p1

Access Restrictions
Application Required
Access Instructions
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Associated Publications
Data Type
Equipment Used
Illumina HiSeq 2500
Software Used
SRA Toolkit
Dataset Format(s)
FASTQ, SRA
Data Tool(s)
WXS
Dataset Size
375.17 GB
Data Catalog Record Updated
2021-10-14