Genomic and Transcriptional Changes in IFN γ Pathway Genes are Putative Biomarkers of Response to Ipilimumab Immunotherapy in Melanoma Patients.

Genomic and Transcriptional Changes in IFNγ Pathway Genes are Putative Biomarkers of Response to Ipilimumab Immunotherapy in Melanoma Patients. Expert Rev Clin Immunol. 2020 Nov 05;: Authors: Hargadon KM, Győrffy B, McGee TJ Abstract Evaluation of: Gao J, Shi LZ, Zhao H et al. Loss of IFN-γ pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy. Cell 167(2), 397-404 (2016). Tumor resistance to immune checkpoint inhibitors limits therapeutic efficacy in many cancer patients. The study by Gao et al. highlighted herein describes a fundamental mechanism by which melanoma escapes the CTLA-4-targeting drug ipilimumab, the first FDA-approved immune checkpoint inhibitor for cancer. This work describes genomic alterations to IFNγ signaling pathway components as a mechanism of melanoma resistance to ipilimumab and has spawned several studies documenting the significance of this pathway to the efficacy of immunotherapy. The authors highlight new analysis of TCGA RNA-seq data that both support and extend the relevance of the IFNγ pathway to CTLA-4 checkpoint blockade as first introduced by this seminal paper, and the authors discuss the relevance of these collective findings to the future of cancer immunotherapy. PMID: 33151785 [PubMed - as supplied by publisher]
Source: Expert Review of Clinical Immunology - Category: Allergy & Immunology Tags: Expert Rev Clin Immunol Source Type: research