FcγR-Mediated Trogocytosis 2.0: Revisiting History Gives Rise to a Unifying Hypothesis

Overview

Journal Antibodies (Basel)

Date 2022 Jul 27

PMID 35892705

Authors

Margaret A Lindorfer

Ronald P Taylor

Affiliations

Soon will be listed here.

Abstract

There is increasing interest in the clinical implications and immunology of trogocytosis, a process in which the receptors on acceptor cells remove and internalize cognate ligands from donor cells. We have reported that this phenomenon occurs in cancer immunotherapy, in which cells that express FcγR remove and internalize CD20 and bound mAbs from malignant B cells. This process can be generalized to include other reactions including the immune adherence phenomenon and antibody-induced immunosuppression. We discuss in detail FcγR-mediated trogocytosis and the evidence supporting a proposed predominant role for liver sinusoidal endothelial cells via the action of the inhibitory receptor FcγRIIb2. We describe experiments to test the validity of this hypothesis. The elucidation of the details of FcγR-mediated trogocytosis has the potential to allow for the development of novel therapies that can potentially block or enhance this reaction, depending upon whether the process leads to unfavorable or positive biological effects.

Citing Articles

Target cell adhesion limits macrophage phagocytosis and promotes trogocytosis.

Rollins K, Fiaz S, Morrissey M bioRxiv. 2025; .

PMID: 39975079 PMC: 11839035. DOI: 10.1101/2025.02.06.636906.

Receptor transfer between immune cells by autoantibody-enhanced, CD32-driven trogocytosis is hijacked by HIV-1 to infect resting CD4 T cells.

Albanese M, Chen H, Gapp M, Muenchhoff M, Yang H, Peterhoff D Cell Rep Med. 2024; 5(4):101483.

PMID: 38579727 PMC: 11031382. DOI: 10.1016/j.xcrm.2024.101483.

Effectiveness and safety of amivantamab in EGFR exon 20 insertion (E20I) mutations in non-small cell lung cancer (NSCLC).

Choi D, Jung H, Park S, Sun J, Ahn J, Ahn M Transl Lung Cancer Res. 2024; 12(12):2448-2459.

PMID: 38205202 PMC: 10775014. DOI: 10.21037/tlcr-23-643.

Macrophage-mediated trogocytosis contributes to destroying human schistosomes in a non-susceptible rodent host, Microtus fortis.

Shen J, Zhao S, Peng M, Li Y, Zhang L, Li X Cell Discov. 2023; 9(1):101.

PMID: 37794085 PMC: 10550985. DOI: 10.1038/s41421-023-00603-6.

Antibody-mediated phagocytosis in cancer immunotherapy.

Van Wagoner C, Rivera-Escalera F, Jaimes-Delgadillo N, Chu C, Zent C, Elliott M Immunol Rev. 2023; 319(1):128-141.

PMID: 37602915 PMC: 10615698. DOI: 10.1111/imr.13265.

References

Ganesan L, Kim J, Wu Y, Mohanty S, Phillips G, Birmingham D . FcγRIIb on liver sinusoidal endothelium clears small immune complexes. J Immunol. 2012; 189(10):4981-8. PMC: 4381350. DOI: 10.4049/jimmunol.1202017. View

Beurskens F, Lindorfer M, Farooqui M, Beum P, Engelberts P, Mackus W . Exhaustion of cytotoxic effector systems may limit monoclonal antibody-based immunotherapy in cancer patients. J Immunol. 2012; 188(7):3532-41. PMC: 3311731. DOI: 10.4049/jimmunol.1103693. View

Sullivan H, Gerner-Smidt C, Nooka A, Arthur C, Thompson L, Mener A . Daratumumab (anti-CD38) induces loss of CD38 on red blood cells. Blood. 2017; 129(22):3033-3037. PMC: 5454337. DOI: 10.1182/blood-2016-11-749432. View

Zent C, Elliott M . Maxed out macs: physiologic cell clearance as a function of macrophage phagocytic capacity. FEBS J. 2016; 284(7):1021-1039. PMC: 5378628. DOI: 10.1111/febs.13961. View

Skopelja-Gardner S, Jones J, Hamilton B, Danilov A, Rigby W . Role for ZAP-70 Signaling in the Differential Effector Functions of Rituximab and Obinutuzumab (GA101) in Chronic Lymphocytic Leukemia B Cells. J Immunol. 2017; 199(4):1275-1282. DOI: 10.4049/jimmunol.1602105. View

Maier C, Mener A, Patel S, Jajosky R, Bennett A, Arthur C . Antibody-mediated immune suppression by antigen modulation is antigen-specific. Blood Adv. 2018; 2(21):2986-3000. PMC: 6234375. DOI: 10.1182/bloodadvances.2018018408. View

Fitzpatrick E, Wang J, Strome S . Engineering of Fc Multimers as a Protein Therapy for Autoimmune Disease. Front Immunol. 2020; 11:496. PMC: 7109252. DOI: 10.3389/fimmu.2020.00496. View

Velmurugan R, Challa D, Ram S, Ober R, Ward E . Macrophage-Mediated Trogocytosis Leads to Death of Antibody-Opsonized Tumor Cells. Mol Cancer Ther. 2016; 15(8):1879-89. PMC: 4975628. DOI: 10.1158/1535-7163.MCT-15-0335. View

Miot S, Marfurt J, Lach-Trifilieff E, Gonzalez-Rubio C, Lopez-Trascasa M, Sadallah S . The mechanism of loss of CR1 during maturation of erythrocytes is different between factor I deficient patients and healthy donors. Blood Cells Mol Dis. 2002; 29(2):200-12. DOI: 10.1006/bcmd.2002.0559. View

10.

Zhao S, Zhang L, Xiang S, Hu Y, Wu Z, Shen J . Gnawing Between Cells and Cells in the Immune System: Friend or Foe? A Review of Trogocytosis. Front Immunol. 2022; 13:791006. PMC: 8850298. DOI: 10.3389/fimmu.2022.791006. View

11.

Bhandari S, Larsen A, McCourt P, Smedsrod B, Sorensen K . The Scavenger Function of Liver Sinusoidal Endothelial Cells in Health and Disease. Front Physiol. 2021; 12:757469. PMC: 8542980. DOI: 10.3389/fphys.2021.757469. View

12.

McBride H, Jassem S, Chow V, Kanakaraj P, Lebrec H, Kuhns S . Non-clinical similarity of biosimilar ABP 798 with rituximab reference product. Biologicals. 2021; 72:42-53. DOI: 10.1016/j.biologicals.2021.05.002. View

13.

Schreiber A, Frank M . Role of antibody and complement in the immune clearance and destruction of erythrocytes. I. In vivo effects of IgG and IgM complement-fixing sites. J Clin Invest. 1972; 51(3):575-82. PMC: 302163. DOI: 10.1172/JCI106846. View

14.

Oostindie S, van der Horst H, Lindorfer M, Cook E, Tupitza J, Zent C . CD20 and CD37 antibodies synergize to activate complement by Fc-mediated clustering. Haematologica. 2019; 104(9):1841-1852. PMC: 6717598. DOI: 10.3324/haematol.2018.207266. View

15.

Grandjean C, Montalvao F, Celli S, Michonneau D, Breart B, Garcia Z . Intravital imaging reveals improved Kupffer cell-mediated phagocytosis as a mode of action of glycoengineered anti-CD20 antibodies. Sci Rep. 2016; 6:34382. PMC: 5048169. DOI: 10.1038/srep34382. View

16.

Sullivan H, Arthur C, Thompson L, Patel S, Stowell S, Hendrickson J . Anti-RhD reduces levels of detectable RhD antigen following anti-RhD infusion. Transfusion. 2018; 58(2):542-544. PMC: 8928237. DOI: 10.1111/trf.14452. View

17.

Richardson S, Crowther C, Mkhize N, Morris L . Measuring the ability of HIV-specific antibodies to mediate trogocytosis. J Immunol Methods. 2018; 463:71-83. DOI: 10.1016/j.jim.2018.09.009. View

18.

Matlung H, Babes L, Zhao X, Van Houdt M, Treffers L, van Rees D . Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis. Cell Rep. 2018; 23(13):3946-3959.e6. DOI: 10.1016/j.celrep.2018.05.082. View

19.

Alari-Pahissa E, Ataya M, Moraitis I, Campos-Ruiz M, Altadill M, Muntasell A . NK cells eliminate Epstein-Barr virus bound to B cells through a specific antibody-mediated uptake. PLoS Pathog. 2021; 17(8):e1009868. PMC: 8409624. DOI: 10.1371/journal.ppat.1009868. View

20.

Ricart A . Antibody-drug conjugates of calicheamicin derivative: gemtuzumab ozogamicin and inotuzumab ozogamicin. Clin Cancer Res. 2011; 17(20):6417-27. DOI: 10.1158/1078-0432.CCR-11-0486. View