Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer Open R B Birge1,10, S Boeltz2,10, S Kumar1,10, J Carlson3,10, J Wanderley4,10, D Calianese1,10, M Barcinski5,10, R A Brekken6,7,10, X Huang6,7,10, J T Hutchins3,10, B Freimark3,10, C Empig3,10, J Mercer8,10, A J Schroit9,10, G Schett2,10 and M Herrmann2,10 1Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers New Jersey Medical School, 205 South Orange Ave, Newark, NJ 07103, USA 2Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), University Hospital Erlangen, 91054 Erlangen, Germany 3Peregrine Pharmaceuticals, 14282 Franklin Avenue, Tustin, CA 92780, USA 4Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil 5Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil 6Division of Surgical Oncology, Department of Surgery, Hamon Center for Therapeutic Oncology Research, Dallas, TX 75390-8593, USA 7Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8593, USA 8Medical Research Council Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK 9Simmons Cancer Center and the Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA 10These authors contributed equally to this work. The large amount of evidence obtained with AnxA5 and PS-targeting antibodies supports the notion that PS is a fundamental immune checkpoint akin to or upstream of the CTLA4 and PD-1/PD-L1 checkpoints. Late-stage clinical trials evaluating the PS-targeting antibody, bavituximab, are in progress in multiple oncology indications, while agents targeting PS receptors are in various stages of pre-clinical and clinical development. .. .. Conflict of interest JC, JTH, BF, and CE are paid employees of Peregrine Pharmaceuticals. RAB receives funding from and is a consultant for Peregrine Pharmaceuticals. MH wants to disclose the involvement in Patent Application EP1356818 A3 filed at the European Patent Office in 1995 and entitled ‘Drug, in particular for modulating the immunological response for the control of viruses, tumors, bacteria, and parasites’. This patent application has already expired. Peregrine Pharmaceuticals, Inc., is the owner or exclusive licensee of hundreds of unexpired worldwide patents broadly covering compositions that target PS and various methods of use, including to treat cancer and viral infections. The remaining authors declare no conflict of interests. http://www.nature.com/cdd/journal/v23/n6/full/cdd201611a.html