A molecule that helps cancer cells evade programmed self-destruction, an internal source of death, might also help malignant cells hide from the immune system, an external source of death.
A new study by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) shows that a molecule called nuclear factor kappa B (NF-kB) helps cancer cells by suppressing the immune system’s ability to detect and destroy them.
The molecule regulates genes that suppress immune surveillance mechanisms, including the production of cells that inhibit the immune response.
The research suggests that immune therapy for cancer might be more effective if combined with drugs that inhibit NF-kB. They also provide new details about how interactions between cancer cells and noncancer cells assist tumor growth.
The findings are published in the journal Cell Reports.
“We’ve long known that NF-kB promotes cancer development by subverting apoptosis, an internal safety mechanism that otherwise would cause cancer cells to self-destruct,” says principal investigator Denis Guttridge, PhD, professor of molecular virology, immunology and medical genetics and of molecular and cellular biochemistry.
“This study shows that NF-kB might coordinate a network of immune-suppressor genes whose products enable tumor cells to evade adaptive immunity,” he adds. “Therefore, inhibiting NF-kB will might make tumor cells more vulnerable to elimination by the immune system.”
A 2009 study by the same researchers showed that NF-kB helps normal cells in DNA repair, which may prevent them from harming the body. However, it is hard to understand why such a molecule might act differently in cancer cells, where NF-kB is typically always in an active state.
For this study, Guttridge, first author David J. Wang, who developed many of the study’s concepts, and their colleagues monitored NF-kB activity during tumor development using mouse embryonic fibroblasts and two mouse models. Key technical findings include:
During early tumor development, macrophages – innate immune cells – migrate into the tumor;
NF-kB enables cancer cells to survive the pro-apoptotic influence of tumor necrosis factor that is released by tumor infiltrating macrophages;
NF-kB may also regulate a number of genes related to immune suppression, particularly TGF-beta, IL-10, GM-CSF, G-CSF and VEGF.
In cancer cells with active NF-kB, shutting down TGF-beta expression removed its immune suppressive influence and delayed tumor growth, evidence that TGF-beta is a gene regulated by NF-kB that contributes to tumor development.
“Overall, our findings demonstrate that NF-kB might play a pivotal role in enabling cells to evade surveillance by both innate and adaptive immune cells,” Guttridge says.
Funding from the NIH/National Cancer Institute (grant CA140158) supported this research.
Other Ohio State researchers involved in this study were Nivedita M. Ratnam and John C. Byrd.
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only four centers funded by the NCI to conduct both phase I and phase II clinical trials. The NCI recently rated Ohio State’s cancer program as “exceptional,” the highest rating given by NCI survey teams. As the cancer program’s 228-bed adult patient-care component, The James is a “Top Hospital” as named by the Leapfrog Group and one of the top cancer hospitals in the nation as ranked by U.S.News & World Report.
Contact: Darrell E. Ward, Wexner Medical Center Public Affairs and Media Relations,
614-293-3737, or Darrell.Ward@osumc.edu
Darrell E. Ward | Eurek Alert!
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
Pollen taxi for bacteria
18.07.2018 | Technische Universität München
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
18.07.2018 | Materials Sciences
18.07.2018 | Life Sciences
18.07.2018 | Health and Medicine