CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes.
Antibody-dependent cellular cytotoxicity (ADCC) is exerted by immune cells expressing surface Fcγ receptors (FcγRs) against cells coated with antibody, such as virus-infected or transformed cells. CD16, the FcγRIIIA, is essential for ADCC by NK cells, and is also expressed by a subset of human blood monocytes. We found that human CD16- expressing monocytes have a broad spectrum of ADCC capacities and can kill cancer cell lines, primary leukemic cells and hepatitis B virus-infected cells in the presence of specific antibodies. Engagement of CD16 on monocytes by antibody bound to target cells activated β2-integrins and induced TNFα secretion. In turn, this induced TNFR expression on the target cells, making them susceptible to TNFα-mediated cell death. Treatment with TLR agonists, DAMPs or cytokines, such as IFNγ, further enhanced ADCC. Monocytes lacking CD16 did not exert ADCC but acquired this property after CD16 expression was induced by either cytokine stimulation or transient transfection. Notably, CD16+ monocytes from patients with leukemia also exerted potent ADCC. Hence, CD16+ monocytes are important effectors of ADCC, suggesting further developments of this property in the context of cellular therapies for cancer and infectious diseases.
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), 8A Biomedical Grove, #04-06, Immunos, Singapore 138648, Singapore.
Wei Hseun
WH
Yeap
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), 8A Biomedical Grove, #04-06, Immunos, Singapore 138648, Singapore.
Kok Loon
KL
Wong
Department of Pediatrics, National University of Singapore, Centre for Translational Medicine, 14 Medical Drive Singapore 117599, Singapore.
Noriko
N
Shimasaki
Department of Haematology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore.
Esmeralda Chi Yuan
EC
Teo
Department of Haematology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore.
Jeffrey Kim Siang
JK
Quek
Department of Haematology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore.
Hao Xiang
HX
Yong
Department of Haematology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore.
Colin Phipps
CP
Diong
Singapore Institute for Clinical Sciences, Brenner Centre for Molecular Medicine, 30 Medical Drive, Singapore 117609, Singapore.|Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
Antonio
A
Bertoletti
Department of Haematology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore.
Yeh Ching
YC
Linn
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), 8A Biomedical Grove, #04-06, Immunos, Singapore 138648, Singapore.
Siew Cheng
SC
Wong
Ann Oncol. 2011 Jun;22(6):1302-7
21109570
J Exp Med. 2000 Aug 21;192(4):565-70
10952726
Nat Immun Cell Growth Regul. 1988;7(5-6):266-79
3146697
Cancer Res. 2003 Sep 1;63(17):5595-600
14500400
Proc Natl Acad Sci U S A. 2015 May 12;112(19):6140-5
25918390
J Virol. 2011 Mar;85(5):1935-42
21159876
J Exp Med. 2004 Jun 21;199(12):1659-69
15210744
Cytometry. 1995 Jun 15;22(2):103-10
7587740
Arthritis Res Ther. 2013 Oct 01;15(5):R139
24286519
Blood. 2011 Aug 4;118(5):e16-31
21653326
Exp Hematol. 2010 Mar;38(3):213-21
20056126
Cancer Res. 2012 Mar 15;72(6):1407-15
22258454
Clin Exp Immunol. 2011 Apr;164(1):57-65
21361908
Int J Cancer. 2011 Jun 1;128(11):2663-72
20715106
Leukemia. 2005 Jan;19(1):69-76
15526027
J Cell Biochem. 1991 Apr;45(4):381-90
1675219
J Immunol. 2010 Jan 1;184(1):512-20
19949082
Blood. 2002 Aug 15;100(4):1502-4
12149240
Inflamm Bowel Dis. 2007 May;13(5):566-72
17260384
Oncotarget. 2016 Jan 12;7(2):2070-9
26655503
J Clin Oncol. 2009 Mar 1;27(7):1122-9
19164213
Nat Med. 2000 Apr;6(4):443-6
10742152
Immunology. 1997 May;91(1):104-8
9203972
Nature. 2002 Jul 11;418(6894):191-5
12110890
Dis Esophagus. 2010 Nov;23(8):675-81
20545975
J Immunol. 2015 Mar 15;194(6):2786-95
25667415
J Immunol. 1998 Feb 1;160(3):1427-35
9570563
Clin Immunol. 2011 May;139(2):122-32
21300572
J Immunol. 1990 May 1;144(9):3444-8
2139455
Nat Rev Cancer. 2012 Mar 22;12(4):278-87
22437872
Nat Rev Immunol. 2010 May;10(5):301-16
20414204
PLoS One. 2012;7(9):e45478
23029038
Proc Natl Acad Sci U S A. 1987 Feb;84(4):1005-9
3029758
Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3378-83
17360654
Br J Cancer. 2006 Jan 30;94(2):259-67
16404427
Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19396-401
20974962
J Clin Oncol. 2008 Apr 10;26(11):1789-96
18347005
Int J Cancer. 1997 Jun 11;71(6):1086-90
9185715
Annu Rev Immunol. 2008;26:421-52
18303997
Cancer Res. 1986 Nov;46(11):5947-52
3756932
Cell Immunol. 1999 Dec 15;198(2):103-10
10648124
J Immunol. 2005 Aug 1;175(3):1636-42
16034103
Neoplasia. 2009 Jul;11(7):662-71
19568411
J Exp Med. 1980 Jul 1;152(1):198-208
6995553
Clinics (Sao Paulo). 2006 Jun;61(3):203-8
16832552
Drugs. 2010 Jul 30;70(11):1445-76
20614951
J Immunol. 2008 Nov 15;181(10):6829-36
18981101
J Leukoc Biol. 2008 Jun;83(6):1423-30
18372339
J Biol Chem. 2003 Nov 14;278(46):45720-9
12941957
Breast Cancer Res Treat. 2012 Dec;136(3):659-71
23065032
J Immunol. 1992 Jan 1;148(1):169-76
1530794
Immunity. 2011 Dec 23;35(6):932-44
22169040
Immunology. 1999 Jul;97(3):429-37
10447764
Clin Transl Sci. 2014 Feb;7(1):82-6
24528902
J Clin Oncol. 2003 Nov 1;21(21):3940-7
12975461
Lung Cancer. 2008 Jan;59(1):32-40
17825949
Cancer Res. 2012 Oct 15;72(20):5428-9; author reply 5430
23047870
Immunogenetics. 2002 Oct;54(7):463-8
12389094