Transcriptional mechanisms of resistance to anti-PD-1 therapy. Homo sapiens

Gene expression in 10 skin metastases from a patient with melanoma who had been treated with anti-PD-1 (Nivolumab) therapy was measured. Differences in gene expression between the lesions which responded to the treatment (n = 6) and the lesions which progressed (n = 4) were analyzed. Expression of certain genes associated with the extracellular matrix and with neutrophil function was found to be higher in the metastases which progressed. Insight into the biology governing response to immunotherapy may lead to improved rationally designed therapies, and to biomarkers for selecting patients who are more likely to benefit from these treatments. Overall design: Gene expression profiling was performed on total RNA extracted from 10 formalin-fixed paraffin-embedded (FFPE) separate skin metastasis specimens taken from one patient, postmortem. 6 of these metastases had regressed after anti-PD-1 therapy, and 4 had progressed. Gene expression levels were compared between these two groups of samples. Details of the design, and the gene signatures found are given in the paper associated with this GEO Series: 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 Favarov, 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, and Suzanne L. Topalian, "Transcriptional mechanisms of resistance to anti-PD-1 therapy," Clinical Cancer Research, Published OnlineFirst February 13, 2017, doi: 10.1158/1078-0432.CCR-17-0270