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Supplementary Table S3 from Transcriptional Mechanisms of Resistance to Anti–PD-1 Therapy

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posted on 2023-03-31, 19:31 authored by Maria L. Ascierto, Alvin Makohon-Moore, Evan J. Lipson, Janis M. Taube, Tracee L. McMiller, Alan E. Berger, Jinshui Fan, Genevieve J. Kaunitz, Tricia R. Cottrell, Zachary A. Kohutek, Alexander Favorov, Vladimir Makarov, Nadeem Riaz, Timothy A. Chan, Leslie Cope, Ralph H. Hruban, Drew M. Pardoll, Barry S. Taylor, David B. Solit, Christine A. Iacobuzio-Donahue, Suzanne L. Topalian

140 Illumina probes corresponding to138 unique genes differentially expressed in regressing (R) vs. progressing (P) cutaneous metastases based on whole genome microarray analysis (fold change magnitude {greater than or equal to}1.7, p value {less than or equal to}0.05 )

Funding

Melanoma Research Alliance

Bloomberg~Kimmel Institute

Barney Family Foundation

Melanoma of Delaware

Laverna Hahn Charitable Trust

National Cancer Institute

Memorial Sloan-Kettering Cancer Center

Starr Cancer Consortium

Pershing Square Sohn Cancer Research Foundation

Immunogenomics and Precision Oncology Platform

Center for Molecular Oncology

History

ARTICLE ABSTRACT

Purpose: To explore factors associated with response and resistance to anti–PD-1 therapy, we analyzed multiple disease sites at autopsy in a patient with widely metastatic melanoma who had a heterogeneous response.Materials and Methods: Twenty-six melanoma specimens (four premortem, 22 postmortem) were subjected to whole exome sequencing. Candidate immunologic markers and gene expression were assessed in 10 cutaneous metastases showing response or progression during therapy.Results: The melanoma was driven by biallelic inactivation of NF1. All lesions had highly concordant mutational profiles and copy number alterations, indicating linear clonal evolution. Expression of candidate immunologic markers was similar in responding and progressing lesions. However, progressing cutaneous metastases were associated with overexpression of genes associated with extracellular matrix and neutrophil function.Conclusions: Although mutational and immunologic differences have been proposed as the primary determinants of heterogeneous response/resistance to targeted therapies and immunotherapies, respectively, differential lesional gene expression profiles may also dictate anti–PD-1 outcomes. Clin Cancer Res; 23(12); 3168–80. ©2017 AACR.See related commentary by Wilmott et al., p. 2921