Biomarkers
Expression levels of a panel of inflammation-related mRNAs could help predict responses to PD-1 blockade in cancer. In tumor samples from 220 patients with nine different cancers, profiling of 680 genes for differential expression before and after treatment with the anti-PD-1 mAb Keytruda pembrolizumab identified 18 inflammation-related genes -- including chemokine CC motif ligand 5 (RANTES; CCL5), CXC chemokine receptor 6 (CXCR6) and signal transducer and activator of transcription 1 (STAT1) -- whose changes in expression were associated with response to Keytruda. In an independent cohort of 96 head and neck cancer patients, the mRNA expression panel predicted response to Keytruda with greater accuracy than PD-L1 protein expression, a conventional marker of response to anti-PD-1 mAbs. Next steps by NanoString Technologies Inc. include developing a clinical diagnostic assay, and next steps by Merck & Co. Inc. include using the mRNA panel and other markers to elucidate molecular features of response and non-response to Keytruda monotherapy...