Learning from PD-1 Resistance: New Combination Strategies Xia Bu, Kathleen M. Mahoney, Gordon J. Freeman  Trends in Molecular Medicine  Volume 22, Issue 6, Pages 448-451 (June 2016) DOI: 10.1016/j.molmed.2016.04.008 Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 1 The Innate PD-1 Resistance (IPRES) Signature. Data from the study by Hugo et al. reveal upregulated expression of gene sets associated with wound healing, angiogenesis, hypoxia, TGF-beta signaling, epithelial–mesenchymal transition (EMT), as well as cell adhesion and extracellular matrix organization in nonresponding melanoma tumors from patients undergoing anti-PD-1 treatment. Nonresponder tumors express less CDH1 (E-cadherin, a marker of differentiated epithelia) than responder tumors. The IPRES signature includes genes involved in immunosuppression (IL10) and angiogenesis (VEGFA, VEGFC, FLT1, and ANGPT2), monocyte and macrophage chemotaxis (CCL2, CCL7, CCL8, and CCL13) and EMT (AXL, ROR2, WNT5A, LOXL2, TWIST2, TAGLN, and FAP). Abbreviations: DC, dendritic cells; MDSC, myeloid-derived suppressor cells; VEGFR, vascular endothelial growth factor receptor. Trends in Molecular Medicine 2016 22, 448-451DOI: (10.1016/j.molmed.2016.04.008) Copyright © 2016 Elsevier Ltd Terms and Conditions