PMID- 36389667
OWN - NLM
STAT- MEDLINE
DCOM- 20221121
LR  - 20221121
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Dual checkpoint blockade of CD47 and LILRB1 enhances CD20 antibody-dependent 
      phagocytosis of lymphoma cells by macrophages.
PG  - 929339
LID - 10.3389/fimmu.2022.929339 [doi]
LID - 929339
AB  - Antibody-dependent cellular phagocytosis (ADCP) by macrophages, an important 
      effector function of tumor targeting antibodies, is hampered by 'Don t Eat Me!' 
      signals such as CD47 expressed by cancer cells. Yet, human leukocyte antigen 
      (HLA) class I expression may also impair ADCP by engaging leukocyte 
      immunoglobulin-like receptor subfamily B (LILRB) member 1 (LILRB1) or LILRB2. 
      Analysis of different lymphoma cell lines revealed that the ratio of CD20 to HLA 
      class I cell surface molecules determined the sensitivity to ADCP by the 
      combination of rituximab and an Fc-silent variant of the CD47 antibody magrolimab 
      (CD47-IgGsigma). To boost ADCP, Fc-silent antibodies against LILRB1 and LILRB2 were 
      generated (LILRB1-IgGsigma and LILRB2-IgGsigma, respectively). While LILRB2-IgGsigma was not 
      effective, LILRB1-IgGsigma significantly enhanced ADCP of lymphoma cell lines when 
      combined with both rituximab and CD47-IgGsigma. LILRB1-IgGsigma promoted serial 
      engulfment of lymphoma cells and potentiated ADCP by non-polarized M0 as well as 
      polarized M1 and M2 macrophages, but required CD47 co-blockade and the presence 
      of the CD20 antibody. Importantly, complementing rituximab and CD47-IgGsigma, 
      LILRB1-IgGsigma increased ADCP of chronic lymphocytic leukemia (CLL) or lymphoma 
      cells isolated from patients. Thus, dual checkpoint blockade of CD47 and LILRB1 
      may be promising to improve antibody therapy of CLL and lymphomas through 
      enhancing ADCP by macrophages.
CI  - Copyright (c) 2022 Zeller, Lutz, Munnich, Windisch, Hilger, Herold, Tahiri, Banck, 
      Weigert, Moosmann, von Bergwelt-Baildon, Flamann, Bruns, Wichmann, Baumann, 
      Valerius, Schewe, Peipp, Rosner, Humpe and Kellner.
FAU - Zeller, Tobias
AU  - Zeller T
AD  - Division of Transfusion Medicine, Cell Therapeutics and Haemostaseology, 
      University Hospital, LMU Munich, Munich, Germany.
FAU - Lutz, Sebastian
AU  - Lutz S
AD  - Division of Transfusion Medicine, Cell Therapeutics and Haemostaseology, 
      University Hospital, LMU Munich, Munich, Germany.
FAU - Munnich, Ira A
AU  - Munnich IA
AD  - Division of Transfusion Medicine, Cell Therapeutics and Haemostaseology, 
      University Hospital, LMU Munich, Munich, Germany.
FAU - Windisch, Roland
AU  - Windisch R
AD  - Division of Transfusion Medicine, Cell Therapeutics and Haemostaseology, 
      University Hospital, LMU Munich, Munich, Germany.
FAU - Hilger, Patricia
AU  - Hilger P
AD  - Division of Transfusion Medicine, Cell Therapeutics and Haemostaseology, 
      University Hospital, LMU Munich, Munich, Germany.
FAU - Herold, Tobias
AU  - Herold T
AD  - Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.
AD  - German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.
AD  - German Cancer Research Center (DKFZ), Heidelberg, Germany.
FAU - Tahiri, Natyra
AU  - Tahiri N
AD  - Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.
FAU - Banck, Jan C
AU  - Banck JC
AD  - Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.
FAU - Weigert, Oliver
AU  - Weigert O
AD  - Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.
AD  - German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.
AD  - German Cancer Research Center (DKFZ), Heidelberg, Germany.
FAU - Moosmann, Andreas
AU  - Moosmann A
AD  - Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.
AD  - DZIF - German Center for Infection Research, Munich, Germany.
AD  - Helmholtz Zentrum Munchen, Munich, Germany.
FAU - von Bergwelt-Baildon, Michael
AU  - von Bergwelt-Baildon M
AD  - Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.
AD  - German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.
AD  - German Cancer Research Center (DKFZ), Heidelberg, Germany.
FAU - Flamann, Cindy
AU  - Flamann C
AD  - Department of Internal Medicine 5, University Hospital Erlangen, Erlangen, 
      Germany.
FAU - Bruns, Heiko
AU  - Bruns H
AD  - Department of Internal Medicine 5, University Hospital Erlangen, Erlangen, 
      Germany.
FAU - Wichmann, Christian
AU  - Wichmann C
AD  - Division of Transfusion Medicine, Cell Therapeutics and Haemostaseology, 
      University Hospital, LMU Munich, Munich, Germany.
FAU - Baumann, Niklas
AU  - Baumann N
AD  - Division of Stem Cell Transplantation and Immunotherapy, Department of Internal 
      Medicine II, Christian Albrechts University and University Hospital 
      Schleswig-Holstein, Kiel, Germany.
FAU - Valerius, Thomas
AU  - Valerius T
AD  - Division of Stem Cell Transplantation and Immunotherapy, Department of Internal 
      Medicine II, Christian Albrechts University and University Hospital 
      Schleswig-Holstein, Kiel, Germany.
FAU - Schewe, Denis M
AU  - Schewe DM
AD  - Department of Pediatrics, Otto-von-Guericke University Magdeburg, Magdeburg, 
      Germany.
FAU - Peipp, Matthias
AU  - Peipp M
AD  - Division of Antibody-Based Immunotherapy, Department of Internal Medicine II, 
      Christian Albrechts University and University Hospital Schleswig-Holstein, Kiel, 
      Germany.
FAU - Rosner, Thies
AU  - Rosner T
AD  - Division of Stem Cell Transplantation and Immunotherapy, Department of Internal 
      Medicine II, Christian Albrechts University and University Hospital 
      Schleswig-Holstein, Kiel, Germany.
FAU - Humpe, Andreas
AU  - Humpe A
AD  - Division of Transfusion Medicine, Cell Therapeutics and Haemostaseology, 
      University Hospital, LMU Munich, Munich, Germany.
FAU - Kellner, Christian
AU  - Kellner C
AD  - Division of Transfusion Medicine, Cell Therapeutics and Haemostaseology, 
      University Hospital, LMU Munich, Munich, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221027
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (CD47 Antigen)
RN  - 0 (Leukocyte Immunoglobulin-like Receptor B1)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 0 (Antibodies)
RN  - 0 (CD47 protein, human)
RN  - 0 (LILRB1 protein, human)
RN  - 0 (Antigens, CD)
SB  - IM
MH  - Humans
MH  - *CD47 Antigen/metabolism
MH  - Leukocyte Immunoglobulin-like Receptor B1/metabolism
MH  - Rituximab/pharmacology/therapeutic use/metabolism
MH  - *Leukemia, Lymphocytic, Chronic, B-Cell/metabolism
MH  - Cell Line, Tumor
MH  - Phagocytosis
MH  - Macrophages
MH  - Antibodies/metabolism
MH  - Antigens, CD/metabolism
PMC - PMC9647079
OTO - NOTNLM
OT  - CD20
OT  - CD47
OT  - LILRB1 (ILT2)
OT  - antibody therapy
OT  - innate immune checkpoint blockade
OT  - lymphoma
OT  - macrophages
OT  - phagocytosis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/11/18 06:00
MHDA- 2022/11/22 06:00
PMCR- 2022/01/01
CRDT- 2022/11/17 12:42
PHST- 2022/04/26 00:00 [received]
PHST- 2022/10/12 00:00 [accepted]
PHST- 2022/11/17 12:42 [entrez]
PHST- 2022/11/18 06:00 [pubmed]
PHST- 2022/11/22 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.929339 [doi]
PST - epublish
SO  - Front Immunol. 2022 Oct 27;13:929339. doi: 10.3389/fimmu.2022.929339. eCollection 
      2022.