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!
One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie
The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy