Hasim et al. showed that immune cells from PD-1 KO mice can, both in vitro and in vivo, acquire surface PD-1 (and other membrane proteins) through contact with PD-1+ tumor cells. Such surface acquisition by cells of membrane parts of other cells (known as trogocytosis) was SLAM receptor-dependent; neither PD-L1 nor Fc receptors were involved. Experiments with PD1+ and PD1- versions of a tumor susceptible to NK-mediated control indicated that trogocytosed PD-1 inhibits NK cell antitumor activity. PD-1 and tumor markers were observed on NK cells in patient samples, suggesting clinical relevance of trogocytosis.
Contributed by Margot O’Toole
ABSTRACT: Trogocytosis modulates immune responses, with still unclear underlying molecular mechanisms. Using leukemia mouse models, we found that lymphocytes perform trogocytosis at high rates with tumor cells. While performing trogocytosis, both Natural Killer (NK) and CD8(+) T cells acquire the checkpoint receptor PD-1 from leukemia cells. In vitro and in vivo investigation revealed that PD-1 on the surface of NK cells, rather than being endogenously expressed, was derived entirely from leukemia cells in a SLAM receptor-dependent fashion. PD-1 acquired via trogocytosis actively suppressed NK cell antitumor immunity. PD-1 trogocytosis was corroborated in patients with clonal plasma cell disorders, where NK cells that stained for PD-1 also stained for tumor cell markers. Our results, in addition to shedding light on a previously unappreciated mechanism underlying the presence of PD-1 on NK and cytotoxic T cells, reveal the immunoregulatory effect of membrane transfer occurring when immune cells contact tumor cells.
Author Info: (1) Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. CI3, University of Ottawa, Ottawa, ON, Canada. (2) Cancer Therapeutics Program, Ottawa Hosp
Author Info: (1) Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. CI3, University of Ottawa, Ottawa, ON, Canada. (2) Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. CI3, University of Ottawa, Ottawa, ON, Canada. (3) Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. CI3, University of Ottawa, Ottawa, ON, Canada. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada. (4) Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci-Bolognetti, Rome, Italy. (5) Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. CI3, University of Ottawa, Ottawa, ON, Canada. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada. (6) Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. CI3, University of Ottawa, Ottawa, ON, Canada. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada. (7) Neuro-Immune Regulome Unit, National Eye Institute, NIH, Bethesda, MD, USA. (8) Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada. (9) Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. CI3, University of Ottawa, Ottawa, ON, Canada. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada. (10) Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. (11) Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (12) Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. (13) Department of Medicine, McGill University, Montral, QC, Canada. Laboratory of Molecular Oncology, Institut de recherches cliniques de Montral, Montral, QC, Canada. (14) Department of Cellular Biotechnology and Hematology, "Sapienza" University of Rome, Rome, Italy. (15) Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci-Bolognetti, Rome, Italy. IRCCS Neuromed, Pozzilli, Italy. (16) School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland. (17) Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. (18) Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci-Bolognetti, Rome, Italy. (19) Department of Medicine, McGill University, Montral, QC, Canada. Laboratory of Molecular Oncology, Institut de recherches cliniques de Montral, Montral, QC, Canada. Department of Medicine, University of Montral, Montral, QC, Canada. (20) Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci-Bolognetti, Rome, Italy. (21) Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada. (22) Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada. (23) Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. CI3, University of Ottawa, Ottawa, ON, Canada. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada.
