PMID- 27670158 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20191120 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 6 DP - 2016 Sep 27 TI - CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes. PG - 34310 LID - 10.1038/srep34310 [doi] LID - 34310 AB - Antibody-dependent cellular cytotoxicity (ADCC) is exerted by immune cells expressing surface Fcgamma receptors (FcgammaRs) against cells coated with antibody, such as virus-infected or transformed cells. CD16, the FcgammaRIIIA, 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 beta2-integrins and induced TNFalpha secretion. In turn, this induced TNFR expression on the target cells, making them susceptible to TNFalpha-mediated cell death. Treatment with TLR agonists, DAMPs or cytokines, such as IFNgamma, 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. FAU - Yeap, Wei Hseun AU - Yeap WH AD - Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), 8A Biomedical Grove, #04-06, Immunos, Singapore 138648, Singapore. FAU - Wong, Kok Loon AU - Wong KL AD - Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), 8A Biomedical Grove, #04-06, Immunos, Singapore 138648, Singapore. FAU - Shimasaki, Noriko AU - Shimasaki N AD - Department of Pediatrics, National University of Singapore, Centre for Translational Medicine, 14 Medical Drive Singapore 117599, Singapore. FAU - Teo, Esmeralda Chi Yuan AU - Teo EC AD - Department of Haematology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore. FAU - Quek, Jeffrey Kim Siang AU - Quek JK AD - Department of Haematology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore. FAU - Yong, Hao Xiang AU - Yong HX AD - Department of Haematology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore. FAU - Diong, Colin Phipps AU - Diong CP AD - Department of Haematology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore. FAU - Bertoletti, Antonio AU - Bertoletti A AD - Singapore Institute for Clinical Sciences, Brenner Centre for Molecular Medicine, 30 Medical Drive, Singapore 117609, Singapore. AD - Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore. FAU - Linn, Yeh Ching AU - Linn YC AD - Department of Haematology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore. FAU - Wong, Siew Cheng AU - Wong SC AD - Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), 8A Biomedical Grove, #04-06, Immunos, Singapore 138648, Singapore. LA - eng PT - Journal Article DEP - 20160927 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 EIN - Sci Rep. 2017 Apr 07;7:46202. PMID: 28387358 PMC - PMC5037471 EDAT- 2016/09/28 06:00 MHDA- 2016/09/28 06:01 PMCR- 2016/09/27 CRDT- 2016/09/28 06:00 PHST- 2016/03/24 00:00 [received] PHST- 2016/09/12 00:00 [accepted] PHST- 2016/09/28 06:00 [entrez] PHST- 2016/09/28 06:00 [pubmed] PHST- 2016/09/28 06:01 [medline] PHST- 2016/09/27 00:00 [pmc-release] AID - srep34310 [pii] AID - 10.1038/srep34310 [doi] PST - epublish SO - Sci Rep. 2016 Sep 27;6:34310. doi: 10.1038/srep34310.