Related Experiment Video

Updated: Jun 23, 2025

Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells
06:55

Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells

Published on: February 22, 2020

18.6K

TLR9 agonism differentially impacts human NK cell-mediated direct killing and antibody-dependent cell-mediated

Anna R Mahr1, Maia M C Bennett-Boehm1,2, Frederik H Rothemejer3,4

  • 1Department of Biology, University of Nebraska at Omaha, Omaha, NE, USA.

Scientific Reports
|June 25, 2024
PubMed

Insights

Toll-like receptor 9 (TLR9) agonism enhances natural killer (NK) cell direct killing of tumor cells but not antibody-dependent cell-mediated cytotoxicity (ADCC). This is potentially due to decreased CD16 expression on NK cells after TLR9 activation.

Area of Science:

  • Immunology
  • Cellular Biology
  • Cancer Research

Background:

  • Natural killer (NK) cells eliminate diseased cells via direct killing or antibody-dependent cell-mediated cytotoxicity (ADCC).
  • Toll-like receptor 9 (TLR9) agonism in peripheral blood mononuclear cells (PBMCs) triggers interferon signaling, activating NK cells.

Purpose of the Study:

  • To investigate an indirect NK cell activation strategy using TLR9 agonism to enhance human NK cell killing function.
  • To determine the differential effects of TLR9 agonism on direct NK cell killing versus ADCC.

Main Methods:

  • Human peripheral blood mononuclear cells (PBMCs) were stimulated with a TLR9 agonist.
  • Activated NK cells were enriched and used in assays to measure tumor cell killing.
  • The Natural Killer-Simultaneous ADCC and Direct Killing Assay (NK-SADKA) was employed to control for donor variability.

Main Results:

  • TLR9 agonism significantly enhanced the direct killing capacity of NK cells.
  • ADCC mediated by NK cells was not increased following TLR9 agonist stimulation.
  • A decrease in NK cell surface CD16 expression was observed post-activation, correlating with impaired ADCC.

Conclusions:

  • TLR9 agonism represents a viable strategy for enhancing direct NK cell cytotoxicity against tumor targets.
  • The impaired ADCC function may be attributed to the downregulation of CD16 on activated NK cells.
  • Further research is warranted to optimize NK cell-based immunotherapies by modulating TLR9 signaling and CD16 expression.
Keywords:
ADCCDirect killingHuman NK cellsImmunophenotypingTLR9 agonist

More Related Videos

Flow Cytometry-based Assay for the Monitoring of NK Cell Functions08:17

Flow Cytometry-based Assay for the Monitoring of NK Cell Functions

Published on: October 30, 2016

21.0K
Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies09:54

Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies

Published on: May 22, 2020

3.5K

Related Concept Videos

Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
889
Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
1.6K
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
775
Immune Surveillance by NK Cells and Phagocytes01:25

Immune Surveillance by NK Cells and Phagocytes

Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
1.4K