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Updated: Mar 14, 2026
Real-time Cytotoxicity Assays in Human Whole Blood
Published on: November 7, 2014
CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes
Wei Hseun Yeap1, Kok Loon Wong1, Noriko Shimasaki2
1Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), 8A Biomedical Grove, #04-06, Immunos, Singapore 138648, Singapore.
Insights
CD16-expressing monocytes are potent immune effectors that kill antibody-coated cancer and infected cells via antibody-dependent cellular cytotoxicity (ADCC). Enhancing CD16 expression boosts ADCC, suggesting therapeutic potential for cancer and infectious diseases.
Area of Science:
- Immunology
- Cellular Biology
- Cancer Research
Background:
- Antibody-dependent cellular cytotoxicity (ADCC) is a key immune mechanism.
- CD16 (FcγRIIIA) mediates ADCC, primarily by NK cells.
- CD16 is also expressed on a subset of human monocytes.
Purpose of the Study:
- To investigate the ADCC capabilities of CD16-expressing human monocytes.
- To explore the mechanisms underlying monocyte-mediated ADCC.
- To assess the therapeutic potential of CD16+ monocytes.
Main Methods:
- Characterization of ADCC activity in CD16+ monocytes against various target cells.
- Analysis of signaling pathways involved in CD16 engagement (e.g., β2-integrin activation, TNFα secretion).
- Investigation of factors enhancing monocyte ADCC and induction of CD16 expression.
Main Results:
- CD16+ monocytes exhibit broad ADCC activity against cancer cells, leukemic cells, and virus-infected cells.
- CD16 engagement activates β2-integrins and induces TNFα secretion, leading to target cell TNFR upregulation and death.
- ADCC can be enhanced by TLR agonists, DAMPs, or cytokines (e.g., IFNγ).
- Monocytes lacking CD16 gain ADCC function upon CD16 induction.
- Leukemic patients' CD16+ monocytes show potent ADCC.
Conclusions:
- CD16+ monocytes are significant effectors of ADCC.
- Monocyte-derived ADCC offers a promising avenue for cellular therapies.
- Targeting CD16+ monocyte function could be beneficial for treating cancer and infectious diseases.
Abstract:
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.
