Related Experiment Video

Updated: Feb 5, 2026

One-step Protocol for Evaluation of the Mode of Radiation-induced Clonogenic Cell Death by Fluorescence Microscopy
06:47

One-step Protocol for Evaluation of the Mode of Radiation-induced Clonogenic Cell Death by Fluorescence Microscopy

Published on: October 23, 2017

11.9K

Natural killer cells induce distinct modes of cancer cell death: Discrimination, quantification, and modulation of

Christian S Backes1, Kim S Friedmann1, Sebastian Mang1

  • 1From the Department of Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, 66421 Homburg, Germany.

The Journal of Biological Chemistry
|September 8, 2018
PubMed

Insights

Natural killer (NK) cells eliminate cancer cells through apoptosis and necrosis. Calcium influx modulates this cell death ratio, offering a new way to enhance anti-tumor immunity.

Area of Science:

  • Immunology
  • Cancer Biology
  • Cellular Biology

Background:

  • Cancer immunotherapy is a rapidly advancing field.
  • Immune cell efficiency in recognizing and eliminating cancer cells is crucial for controlling tumors.
  • Natural killer (NK) cells play a key role in innate immunity against cancer.

Purpose of the Study:

  • To develop a time-resolved single-cell assay to quantify NK cell-mediated cytotoxicity.
  • To investigate the mechanisms and modes of cancer cell death induced by single NK cells.
  • To explore the role of calcium (Ca2+) influx and specific cytotoxic pathways in tuning NK cell function.

Main Methods:

  • Development of a novel time-resolved single-cell assay to monitor NK cell-target cell interactions.
  • Analysis of cancer cell death modes (apoptosis, necrosis, mixed) induced by individual primary human NK cells.
  • Pharmacological inhibition of key cytotoxic pathways: perforin/granzyme and FasL/FasR.
  • Assessment of the impact of Ca2+ influx through Orai channels on NK cell activity.

Main Results:

  • Single NK cells induce cancer cell death via apoptosis, necrosis, and mixed mechanisms.
  • Inhibition of one cytotoxic pathway (perforin/granzyme or FasL/FasR) revealed the parallel activity of the other.
  • Ca2+ influx through Orai channels is critical for regulating NK cell cytotoxic function.
  • The ratio of apoptosis to necrosis in NK cell-induced cancer cell death is controlled by Ca2+ entry magnitude and perforin/granzyme B concentrations.

Conclusions:

  • A new assay allows detailed characterization of single NK cell-mediated killing.
  • NK cell-induced cancer cell death is a complex process involving multiple pathways and modes.
  • Modulating Ca2+ influx and effector molecule concentrations offers a strategy to control the apoptosis/necrosis ratio.
  • This control presents opportunities to enhance tumor microenvironment immunogenicity for improved cancer immunotherapy.
Keywords:
apoptosiscalciumcancercaspasecell deathcellular immune responseimagingimmunologynatural killer cells (NK cells)necrosis (necrotic death)

More Related Videos

Analysis of Human Natural Killer Cell Metabolism09:03

Analysis of Human Natural Killer Cell Metabolism

Published on: June 22, 2020

7.4K
Flow Cytometric Detection of Newly-formed Breast Cancer Stem Cell-like Cells After Apoptosis Reversal11:21

Flow Cytometric Detection of Newly-formed Breast Cancer Stem Cell-like Cells After Apoptosis Reversal

Published on: January 26, 2019

10.4K

Related Concept Videos

Distinctive Features of Adult Stem Cells vs Cancer Stem Cells01:18

Distinctive Features of Adult Stem Cells vs Cancer Stem Cells

A stem cell is an unspecialized cell that can divide without limit as needed and can, under specific conditions, differentiate into specialized cells.
Adult stem cells
Adult stem cells are tissue-specific; hence, they divide to develop the tissue from which they originate. One type of adult stem cell is the epithelial stem cell, which gives rise to the keratinocytes in the multiple layers of epithelial cells in the epidermis of the skin. Adult bone marrow has three distinct types of stem cells:...
4.5K
Stereotypes, Prejudice, and Discrimination02:55

Stereotypes, Prejudice, and Discrimination

Humans are very diverse and although we share many similarities, we also have many differences. The social groups we belong to help form our identities (Tajfel, 1974). These differences may be difficult for some people to reconcile, which may lead to prejudice toward people who are different. Prejudice is a negative attitude and feeling toward an individual based solely on one’s membership in a particular social group (Allport, 1954; Brown, 2010). Prejudice is common against people who...
95.4K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.6K
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
10.1K
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
6.6K
Induced Pluripotent Stem Cells01:13

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
28.1K