The STING of death in T cells

September 5, 2017, Ecole Polytechnique Federale de Lausanne

The cells of the innate immune system use a signaling pathway comprising STING (Stimulator of interferon genes) to detect DNA from invading viruses and fight them. However, it is unknown if STING triggers the same or different responses in cells of the adaptive immune system, such as T cells. EPFL scientists have now shown that T cells have an "unconventional" STING response, which manifests as apoptotic cell death. The work, which may have implications for the treatment T cell-derived malignancies, is published in Nature Communications.

Innate immune system

The innate immune system is our first line of defense, made up of that quickly identify pathogens such as DNA from viruses. To do this, these cells use receptors that can identify nucleic acids—the building blocks of DNA—that in turn activate a signaling molecule called STING.

Once activated, the STING turns on a set of genes that produce signaling molecules (cytokines) that help cells communicate with each other, as well as other cell-activating processes that fight off the infecting pathogen. But what we don't know whether the STING response produces different outcomes between different cell types.

The STING of death

The lab of Andrea Ablasser at EPFL looked at the consequences of the STING pathway in T cells. Their analysis found that STING triggers the expression of BH3-only proteins—well known to be involved in cell death—which induces apoptosis in cells, as opposed to the production of cytokines such as interferons, which stimulate immune responses.

Interestingly, the researchers also found that this pro-apoptotic effect exists in cancerous T cells, such as the ones that cause T-cell lymphomas, which account for about a tenth of non-Hodgkin lymphomas. The EPFL scientists found that delivering a small molecule that activates the STING pathway prevents the growth of T cell-derived tumors in live animals.

The work shows an unanticipated connection between the magnitude of STING signaling and its ability to elicit different responses. This may allow for cell-type-adjusted behaviors in the presence of internal or external insults such as infections or oxidative stress.

The study uncovers a novel, non-immune effect of the STING pathway whereby it induces a different effect in cells of the adaptive immune system (T cells) than its effect in cells of the innate immune system. The fact that this effect is pro-apoptotic and is maintained even in cancerous T cells in vivo open up significant possibilities for treating T-cell lymphomas in the future.

Explore further: Cell senescence is regulated by innate DNA sensing

More information: Muhammet F. Gulen et al, Signalling strength determines proapoptotic functions of STING, Nature Communications (2017). DOI: 10.1038/s41467-017-00573-w

Related Stories

Cell senescence is regulated by innate DNA sensing

July 31, 2017
Cells in the body or in cultures eventually stop replicating. This phenomenon is called "senescence" and is triggered by shortening of telomeres, oxidative stress or genetic damage to the cells, either acute or simply due ...

Danish discovery opens up for new type of immunological treatment of cancer

February 21, 2017
Researchers from Aarhus University have found an important piece of the puzzle leading towards an understanding of how our innate immune system reacts against viral infections and recognises foreign DNA, for example from ...

Researchers describe role of STING protein in development of colorectal cancer

January 1, 2016
A new study published today by researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine (Sylvester) reports on a key finding about the immune system's response to tumor development ...

New class of drugs specifically induces cell death in B cell blood cancers

March 10, 2016
In almost every mammalian cell, you will find the endoplasmic reticulum, a network of continuous membranes responsible for controlling metabolism as well as the folding, assembly and secretion of proteins. Since the endoplasmic ...

Novel immunotherapy approach shows promise in blood cancers

June 2, 2016
A protein known as STING plays a crucial role in the immune system's ability to "sense" cancer by recognizing and responding to DNA from tumor cells. Injection of compounds that activate the STING pathway directly into solid ...

Every step you take: STING pathway key to tumor immunity

November 20, 2014
A recently discovered protein complex known as STING plays a crucial role in detecting the presence of tumor cells and promoting an aggressive anti-tumor response by the body's innate immune system, according to two separate ...

Recommended for you

Obesity and health problems: New research on a safeguard mechanism

March 16, 2018
Obesity and its negative impacts on health - including metabolic syndrome, type-2 diabetes mellitus and cardiovascular complications - are a global pandemic (Taubes, 2009). The worldwide incidence of obesity has more than ...

Immune system 'double agent' could be new ally in cancer fight

March 16, 2018
St. Jude Children's Research Hospital scientists have discovered that an enzyme called TAK1 functions like a "double agent" in the innate immune response, serving as an unexpected regulator of inflammation and cell death. ...

Artificial sweetener Splenda could intensify symptoms in those with Crohn's disease

March 15, 2018
In a study that has implications for humans with inflammatory diseases, researchers from Case Western Reserve University School of Medicine and colleagues have found that, given over a six-week period, the artificial sweetener ...

Researchers identify common biological features of different types of asthma

March 14, 2018
A team of researchers from the NIHR Leicester Biomedical Research Centre - a partnership between Leicester's Hospitals, the University of Leicester and Loughborough University - has identified biological variations in lung ...

Scientists discover treatment target for sepsis

March 14, 2018
In a study published in Nature Communications, Northwestern Medicine scientists demonstrated the key role a molecule called oxPAPC plays in regulating the inflammatory response—findings which could inform the development ...

Researcher creates 'Instagram' of immune system, blending science, technology

March 10, 2018
Being on the cutting edge of science and technology excites Hollings Cancer Center (HCC) researcher Carsten Krieg, Ph.D. Each day, he walks into his lab that houses a mass cytometry machine aptly labeled Helios. Krieg explains ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.