We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
LGC Clinical Diagnostics

Download Mobile App




Newly Discovered Protein Complex Pathway Found to Be Key to Radiation-Induced Antitumor Immunity

By LabMedica International staff writers
Posted on 02 Dec 2014
Print article
A recently discovered protein complex called STimulator of INterferon Genes (STING) plays a key role in detecting the presence of tumor cells and triggers an aggressive antitumor response by the body’s innate immune system.

The two separate studies, published November 20, 2014, in the journal Immunity, both conducted by investigators from the University of Chicago (IL, USA) have key implications for the increasing field of cancer immunotherapy. The findings show that when activated, the STING pathway triggers a natural immune response against the tumor. This includes the generation of chemical signals that help the immune system identify tumor cells and generate specific killer T cells. Moreover, the researchers revealed that targeted high-dose radiation therapy triggers the activation of this pathway, which then stimulates immune-mediated tumor control.

These findings could “enlarge the fraction of patients who respond to immunotherapy with prolonged control of the tumor,” according to a commentary on the studies by the University of Verona’s (Italy) Vincenzo Bronte, MD. “Enhancing the immunogenicity of their cancers might expand the lymphocyte repertoire that is then unleashed by interference with checkpoint blockade pathways,” such as anti-PD-1.

STING is a vital part of the process the immune system relies on to identify threats—such as infections or cancer cells—that are noticeable by the presence of DNA that is damaged or in the wrong place, inside the cell but outside the nucleus. Detection of such “cytosolic” DNA initiates a range of interactions that lead to the STING pathway. Activating the pathway triggers the production of interferon-beta, which in turn warns the immune system to the threat, helps the system detect cancerous or infected cells, and ultimately sends activated T cells into the battle.

“We have learned a great deal recently about what we call checkpoints, the stumbling blocks that prevent the immune system from ultimately destroying cancers,” said Thomas Gajewski, MD, PhD, professor of medicine and pathology at the University of Chicago, and senior author of one of the studies. “Blockade of immune checkpoints, such as with anti-PD-1, is therapeutic in a subset of patients, but many individuals still don’t respond. Understanding the role of the STING pathway provides insights into how we can ‘wake up’ the immune response against tumors. This can be further boosted by checkpoint therapies.”

The two published studies, Dr. Gajewski noted, help push this application forward. In a series of research experiments in mice, both groups found tumor cell-derived DNA could trigger an immune response against tumors. However, when tested in mice that lacked a functional gene for STING, the immune system did not effectively respond. “Innate immune sensing via the host STING pathway is critical for tumor control by checkpoint blockade,” the authors stated in their article. They found potential drugs known as checkpoint inhibitors—such as anti PD-1 or anti PD-L1, which can block an immune response—were not effective in STING-deficient mice. New agents that stimulate the STING pathway are being developed as potential cancer therapeutics.

A second University of Chicago team, led by cancer biologist Yang-Xin Fu, MD, PhD, professor of pathology, and Ralph Weichselbaum, MD, chairman of radiation and cellular oncology and co-director of the Ludwig Center for Metastasis Research, demonstrated that high-dose radiation therapy not only kills targeted cancer cells but the resulting DNA damage fuels a systemic immune response. “This result unifies traditional studies of DNA damage with newly identified DNA sensing of immune responses,” Dr. Fu said. “This is a previously unknown mechanism,” Dr. Weichselbaum added.

In mice that lacked STING, however, there was no therapeutic immune response. The induction of interferons by radiation and consequent cancer cell killing, they conclude, depends on STING-pathway signaling. They did find that combining cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), an earlier step in the STING pathway, with radiation, could greatly enhance the antitumor effectiveness of radiation.

“This opens a new avenue to develop STING-related agonists for patients with radiation-resistant cancers,” Dr. Fu concluded.

Related Links:

University of Chicago


New
Gold Member
Pneumocystis Jirovecii Detection Kit
Pneumocystis Jirovecii Real Time RT-PCR Kit
Antipsychotic TDM AssaysSaladax Antipsychotic Assays
New
Herpes Virus Test
Human Herpes Virus (HHV-6) Real Time PCR Kit
New
Rocking Shaker
HumaRock

Print article

Channels

Clinical Chemistry

view channel
Image: The new saliva-based test for heart failure measures two biomarkers in about 15 minutes (Photo courtesy of Trey Pittman)

POC Saliva Testing Device Predicts Heart Failure in 15 Minutes

Heart failure is a serious condition where the heart muscle is unable to pump sufficient oxygen-rich blood throughout the body. It ranks as a major cause of death globally and is particularly fatal for... Read more

Hematology

view channel
Image: The smartphone technology measures blood hemoglobin levels from a digital photo of the inner eyelid (Photo courtesy of Purdue University)

First-Of-Its-Kind Smartphone Technology Noninvasively Measures Blood Hemoglobin Levels at POC

Blood hemoglobin tests are among the most frequently conducted blood tests, as hemoglobin levels can provide vital insights into various health conditions. However, traditional tests are often underutilized... Read more

Immunology

view channel
Image: Under a microscope, DNA repair is visible as bright green spots (“foci”) in the blue-stained cell DNA. Orange highlights actively growing cancer cells (Photo courtesy of WEHI)

Simple Blood Test Could Detect Drug Resistance in Ovarian Cancer Patients

Every year, hundreds of thousands of women across the world are diagnosed with ovarian and breast cancer. PARP inhibitors (PARPi) therapy has been a major advancement in treating these cancers, particularly... Read more

Microbiology

view channel
Image: HNL Dimer can be a novel and potentially useful clinical tool in antibiotic stewardship in sepsis (Photo courtesy of Shutterstock)

Unique Blood Biomarker Shown to Effectively Monitor Sepsis Treatment

Sepsis remains a growing problem across the world, linked to high rates of mortality and morbidity. Timely and accurate diagnosis, along with effective supportive therapy, is essential in reducing sepsis-related... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.