SIRPα Suppresses Response to Therapeutic Antibodies by Nurse Like Cells From Chronic Lymphocytic Leukemia Patients.
Humans
Antibodies, Monoclonal, Humanized
/ pharmacology
Antigens, CD20
/ immunology
Antigens, Differentiation
/ genetics
Antineoplastic Agents, Immunological
/ pharmacology
CD47 Antigen
/ genetics
Cells, Cultured
Immunity, Innate
/ drug effects
Leukemia, Lymphocytic, Chronic, B-Cell
/ drug therapy
Macrophages
/ drug effects
Phagocytosis
/ drug effects
Protein Tyrosine Phosphatase, Non-Receptor Type 6
/ metabolism
Receptors, Immunologic
/ genetics
Signal Transduction
Syk Kinase
/ metabolism
antibody dependent phagocytosis
antibody resistance 2
chronic lymphocytic leukemia
macrophage
macrophages
nurse-like-cells
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
26
09
2020
accepted:
07
12
2020
entrez:
8
2
2021
pubmed:
9
2
2021
medline:
23
6
2021
Statut:
epublish
Résumé
Targeted antibody therapies improve outcomes for chronic lymphocytic leukemia (CLL) patients. However, resistance often develops. We have previously shown that resistance to therapeutic antibodies, by monocyte derived macrophages (referred to as nurse like cells, NLCs), from CLL patients is characterized by suppression of antibody dependent phagocytosis (ADP). The mechanism(s) contributing to the muted ADP responses remain unresolved. In this regard, an innate immune checkpoint was recently described that uses the CD47:SIRPα axis to suppress phagocytic responses by macrophages. In this study we examine whether the SIRPα axis regulates ADP responses to the anti-CD20 antibody, obinutuzumab, by NLCs. Using siRNA depletion strategies we show that SIRPα is a suppressor of ADP responses. Moreover, we show that this innate immune checkpoint contributes to the resistance phenotype in NLCs derived from CLL patients. Finally, we show that SIRPα suppression is mediated
Identifiants
pubmed: 33552071
doi: 10.3389/fimmu.2020.610523
pmc: PMC7859087
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antigens, CD20
0
Antigens, Differentiation
0
Antineoplastic Agents, Immunological
0
CD47 Antigen
0
CD47 protein, human
0
obinutuzumab
O43472U9X8
Protein Tyrosine Phosphatase, Non-Receptor Type 6
EC 3.1.3.48
Receptors, Immunologic
0
SIRPA protein, human
0
Syk Kinase
EC 2.7.10.2
SYK protein, human
EC 2.7.10.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
610523Informations de copyright
Copyright © 2021 Chen, Burgess, Mapp, Mollee, Gill, Blumenthal and Saunders.
Déclaration de conflit d'intérêts
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.
Références
J Immunol. 2004 Jul 1;173(1):332-9
pubmed: 15210791
N Engl J Med. 2018 Nov 01;379(18):1711-1721
pubmed: 30380386
Leukemia. 2013 Apr;27(5):1172-4
pubmed: 22936013
Mol Cell Biol. 1998 Jul;18(7):4209-20
pubmed: 9632805
Transl Oncol. 2019 Apr;12(4):626-632
pubmed: 30738349
Cancer Discov. 2015 Sep;5(9):915-9
pubmed: 26272491
Nature. 1997 Mar 13;386(6621):181-6
pubmed: 9062191
J Immunol. 2005 Feb 15;174(4):2004-11
pubmed: 15699129
J Immunol. 2016 Jul 15;197(2):644-54
pubmed: 27271569
Leukemia. 2020 Feb;34(2):451-461
pubmed: 31462739
J Biol Chem. 1998 Aug 28;273(35):22719-28
pubmed: 9712903
J Clin Invest. 2014 Feb;124(2):812-23
pubmed: 24430180
Nat Commun. 2020 Jan 29;11(1):581
pubmed: 31996683
Drugs Aging. 2015 Nov;32(11):877-86
pubmed: 26446155
Nat Rev Cancer. 2019 Oct;19(10):568-586
pubmed: 31462760
Blood. 2018 Jun 21;131(25):2745-2760
pubmed: 29540348
Nat Rev Immunol. 2006 Jun;6(6):457-64
pubmed: 16691243
Leukemia. 2020 Feb;34(2):441-450
pubmed: 31455851
J Natl Compr Canc Netw. 2019 Jan;17(1):12-20
pubmed: 30659125
Mol Cell Biol. 1996 Dec;16(12):6887-99
pubmed: 8943344
Blood. 1985 Sep;66(3):490-5
pubmed: 2992636
Trends Biochem Sci. 2003 Jun;28(6):284-93
pubmed: 12826400
Cell. 2010 Sep 3;142(5):699-713
pubmed: 20813259
Blood. 2019 Nov 21;134(21):1796-1801
pubmed: 31751484
J Immunol. 2010 Jun 1;184(11):6529-36
pubmed: 20421638
Blood. 2000 Oct 15;96(8):2655-63
pubmed: 11023495
Oncogene. 2020 Dec 22;:
pubmed: 33353962
Clin Exp Immunol. 2016 Jan;183(1):90-101
pubmed: 26307241
MAbs. 2015;7(2):303-10
pubmed: 25667985
Clin Cancer Res. 2016 Oct 15;22(20):5109-5119
pubmed: 27126995
Oncotarget. 2018 Jul 6;9(52):29944-29956
pubmed: 30042825
Nat Rev Drug Discov. 2012 Mar 30;11(4):311-31
pubmed: 22460124
J Immunol. 2005 Oct 1;175(7):4450-7
pubmed: 16177087
Cancer Immunol Res. 2018 Oct;6(10):1150-1160
pubmed: 30089638
Biochim Biophys Acta Rev Cancer. 2017 Aug;1868(1):176-182
pubmed: 28347751
Oncogene. 2017 Apr 27;36(17):2366-2376
pubmed: 27748757
J Immunother. 2006 Jul-Aug;29(4):388-97
pubmed: 16799334
J Biol Chem. 1998 Apr 10;273(15):9234-42
pubmed: 9535915
J Exp Med. 2001 Apr 2;193(7):855-62
pubmed: 11283158
Leuk Lymphoma. 2020 Nov;61(11):2738-2742
pubmed: 32536228
Blood. 2002 Sep 1;100(5):1852-9
pubmed: 12176909
Blood. 2002 Feb 1;99(3):1030-7
pubmed: 11807009
Leuk Lymphoma. 2011 Jul;52(7):1404-6
pubmed: 21699388
Mol Cell Biol. 1996 Sep;16(9):4735-43
pubmed: 8756631
Nat Commun. 2017 Apr 05;8:14802
pubmed: 28378740
Nature. 2017 Apr 27;544(7651):493-497
pubmed: 28424516
Front Immunol. 2020 Jan 28;11:18
pubmed: 32082311
Cancer Res. 2011 Feb 15;71(4):1374-84
pubmed: 21177380
Cancer Cell. 2015 Apr 13;27(4):473-88
pubmed: 25873171