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!
Microscope measures muscle weakness
16.11.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
Good preparation is half the digestion
16.11.2018 | Max-Planck-Institut für Stoffwechselforschung
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
16.11.2018 | Health and Medicine
16.11.2018 | Life Sciences
16.11.2018 | Life Sciences