When killers become thieves: Trogocytosed PD-1 inhibits NK cells in cancer-Reference-Cited by-同舟云学术

When killers become thieves: Trogocytosed PD-1 inhibits NK cells in cancer

Published:2022-04-15 Issue:15 Volume:8 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Hasim Mohamed S.¹²^ORCID,Marotel Marie¹²^ORCID,Hodgins Jonathan J.¹²³^ORCID,Vulpis Elisabetta⁴,Makinson Olivia J.¹²³^ORCID,Asif Sara¹²³,Shih Han-Yun⁵^ORCID,Scheer Amit K.³^ORCID,MacMillan Olivia¹²³^ORCID,Alonso Felipe G.¹^ORCID,Burke Kelly P.⁶⁷^ORCID,Cook David P.¹^ORCID,Li Rui⁸⁹^ORCID,Petrucci Maria Teresa¹⁰^ORCID,Santoni Angela⁴¹¹,Fallon Padraic G.¹²^ORCID,Sharpe Arlene H.¹³¹⁴^ORCID,Sciumè Giuseppe⁴,Veillette André⁸⁹¹⁵^ORCID,Zingoni Alessandra⁴,Gray Douglas A.¹³,McCurdy Arleigh¹¹⁶^ORCID,Ardolino Michele¹²³^ORCID

Affiliation:

1. Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.

2. CI3, University of Ottawa, Ottawa, ON, Canada.

3. 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. Neuro-Immune Regulome Unit, National Eye Institute, NIH, Bethesda, MD, USA.

6. Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA.

7. Harvard Medical School, Boston, MA, USA.

8. Department of Medicine, McGill University, Montréal, QC, Canada.

9. Laboratory of Molecular Oncology, Institut de recherches cliniques de Montréal, Montréal, QC, Canada.

10. Department of Cellular Biotechnology and Hematology, “Sapienza” University of Rome, Rome, Italy.

11. IRCCS Neuromed, Pozzilli, Italy.

12. School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.

13. Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.

14. Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA, USA.

15. Department of Medicine, University of Montréal, Montréal, QC, Canada.

16. Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference76 articles.

1. What is trogocytosis and what is its purpose?

2. Biting Off What Can Be Chewed: Trogocytosis in Health, Infection, and Disease

3. TCR-Mediated Internalization of Peptide-MHC Complexes Acquired by T Cells

4. T Cells Can Use Either T Cell Receptor or Cd28 Receptors to Absorb and Internalize Cell Surface Molecules Derived from Antigen-Presenting Cells

5. Cutting Edge: CTLs Rapidly Capture Membrane Fragments from Target Cells in a TCR Signaling-Dependent Manner

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