Sahu, Ravi P.Ocana, Jesus A.Harrison, Kathleen A.Ferracini, MatheusTouloukian, Christopher E.Al-Hassani, MohammedSun, LouisLoesch, MathewMurphy, Robert C.Althouse, Sandra K.Perkins, Susan M.Speicher, Paul J.Tyler, Douglas S.Konger, Raymond L.Travers, Jeffrey B.2017-01-042017-01-042014-12-01Sahu, R. P., Ocana, J. A., Harrison, K. A., Ferracini, M., Touloukian, C. E., Al-Hassani, M., … Travers, J. B. (2014). Chemotherapeutic agents subvert tumor immunity by generating agonists of platelet-activating factor. Cancer Research, 74(23), 7069–7078. http://doi.org/10.1158/0008-5472.CAN-14-20431538-7445https://hdl.handle.net/1805/11769Oxidative stress suppresses host immunity by generating oxidized lipid agonists of the platelet-activating factor receptor (PAF-R). Because many classical chemotherapeutic drugs induce reactive oxygen species (ROS), we investigated whether these drugs might subvert host immunity by activating PAF-R. Here, we show that PAF-R agonists are produced in melanoma cells by chemotherapy that is administered in vitro, in vivo, or in human subjects. Structural characterization of the PAF-R agonists induced revealed multiple oxidized glycerophosphocholines that are generated nonenzymatically. In a murine model of melanoma, chemotherapeutic administration could augment tumor growth by a PAF-R-dependent process that could be blocked by treatment with antioxidants or COX-2 inhibitors or by depletion of regulatory T cells. Our findings reveal how PAF-R agonists induced by chemotherapy treatment can promote treatment failure. Furthermore, they offer new insights into how to improve the efficacy of chemotherapy by blocking its heretofore unknown impact on PAF-R activation.en-USPublisher PolicyAntineoplastic AgentsimmunologypharmacologyMelanoma, Experimentaldrug therapyPlatelet Activating FactoragonistsArticle