Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Common cancers evade detection by silencing parts of immune system cells

05.03.2014

Johns Hopkins researchers identify set of genes that can be turned back on and potentially allow for more effective treatment

Johns Hopkins researchers say they have identified a set of genes that appear to predict which tumors can evade detection by the body's immune system, a step that may enable them to eventually target only the patients most likely to respond best to a new class of treatment.

Immune therapy for ovarian, breast and colorectal cancer — treatments that encourage the immune system to attack cancer cells as the foreign invaders they are — has so far had limited success, primarily because the immune system often can't destroy the cancer cells. In a report published online Feb. 16 in the journal Oncotarget, the Johns Hopkins team says it has identified genes that have been repressed through so-called epigenetic changes — modifications that alter the way genes function without changing their DNA sequence — which help the cells to evade the immune system. The researchers were able to reverse these epigenetic changes with the use of an FDA-approved drug, forcing the cancer cells out of hiding and potentially making them better targets for the same immune therapy that in the past may have failed.

"Chemotherapy often works, but in most cases, it eventually stops working," says one of the study leaders, Nita Ahuja, M.D., an associate professor of surgery, oncology and urology at the Johns Hopkins University School of Medicine. "What if we could get the immune system itself to fight the tumors and keep the cancer in check forever? That is the ultimate goal, and this gene panel may get us closer." The other study leader is Cynthia Zahnow, Ph.D., an associate professor of oncology at Johns Hopkins.

... more about:
»Cancer »Medicine »breast »colorectal »genes »therapy

The researchers treated 63 cancer cell lines (26 breast, 14 colorectal and 23 ovarian) with low-dose 5-azacitidine (AZA), an FDA-approved drug for myelodysplastic syndrome, that reverses epigenetic changes by stripping off the methyl group that silences the gene. They identified a panel of 80 biological pathways commonly increased in expression by AZA in all three cancers, finding that 16 of them (20 percent) are related to the immune system. These pathways appeared to be dialed down in the cancer cells, allowing for evasion. After treatment with AZA, the epigenetic changes were reversed, rendering the cancer cells unable to evade the immune system any longer.

The researchers found that these immune system pathways were suppressed in a large number of primary tumors — roughly 50 percent of ovarian cancers studied, 40 percent of colorectal cancers and 30 percent of breast cancers. The findings may be applicable to other cancer types such as lung cancer or melanoma, they say.

After looking in cell lines, the Johns Hopkins team extended their work to human tumor samples. Again they found evidence that these immune system pathways are turned down in some patients and, that these immune genes can be turned back up in a small number of patients with breast and colorectal cancer who had been treated with epigenetic therapies.

"Most of us haven't thought of these common cancers as being immune-driven," Ahuja says. "We haven't held out much hope for immune therapy to work in them because before you can enter cancer cells to knock them down, you have to be able to get inside. They were locked and now we may have identified a key."

The hope is that clinicians could eventually pinpoint which patients with these common cancers would benefit from a dose of AZA followed by an immune therapy that stimulates the immune system to attack cancer cells.

"This would tell us which patients' tumors are hiding from the immune system and will allow us to use all of our tools to flush that cancer out," she says.

While most of the work was done in the lab, Ahuja says her colleagues have already started to put the panel into use in a lung cancer trial. Six patients were treated first with epigenetic therapy followed by immune therapy. Though the sample is small and time has been short, four of the patients have had their cancer suppressed for many months.

"If this works — and we don't know yet if it will — this could have the potential to control someone's cancer for good," she says.

###

Other Johns Hopkins researchers involved in the study include Huili Li, Ph.D.; Katherine B. Chiappinelli, Ph.D.; Angela A. Guzzetta, M.D.; Hariharan Easwaran, Ph.D.; Ray-Whay Chiu Yen, M.S.; Rajita Vatapalli; Michael J. Topper; Jianjun Luo; Roisin M. Connolly, M.B.B.S.; Nilofer S. Azad, M.D.; Vered Stearns, M.D.; Drew M. Pardoll, M.D., Ph. D.; and Stephen B. Baylin, M.D. Researchers from the University of Pittsburgh, the University of Southern California and the University of California-Los Angeles also contributed to the study.

The study was supported by grants from the National Institutes of Health's National Cancer Institute (CA058184 and K23 CA127141), Stand Up To Cancer (SU2C) Epigenetic Dream Team, Hodson Trust, the Samuel Waxman Cancer Research Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, EIF Lee Jeans, the American College of Surgeons/Society of University Surgeons, the Irving Hansen Foundation, the Safeway Foundation and LCOR.

Ahuja and Zahnow both consult for Celgene, the company that makes AZA.

Johns Hopkins Medicine (JHM), headquartered in Baltimore, Maryland, is a $6.7 billion integrated global health enterprise and one of the leading health care systems in the United States. JHM unites physicians and scientists of the Johns Hopkins University School of Medicine with the organizations, health professionals and facilities of The Johns Hopkins Hospital and Health System. JHM's vision, "Together, we will deliver the promise of medicine," is supported by its mission to improve the health of the community and the world by setting the standard of excellence in medical education, research and clinical care. Diverse and inclusive, JHM educates medical students, scientists, health care professionals and the public; conducts biomedical research; and provides patient-centered medicine to prevent, diagnose and treat human illness. JHM operates six academic and community hospitals, four suburban health care and surgery centers, and more than 30 primary health care outpatient sites. The Johns Hopkins Hospital, opened in 1889, was ranked number one in the nation for 21 years in a row by U.S. News & World Report.

Stephanie Desmon |
Further information:
http://www.jhmi.edu

Further reports about: Cancer Medicine breast colorectal genes therapy

More articles from Health and Medicine:

nachricht It don't mean a thing if the brain ain't got that swing
28.07.2015 | University of California - Berkeley

nachricht MSU scientists set sights on glaucoma medication to treat TB
24.07.2015 | Michigan State University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Superfast fluorescence sets new speed record

Plasmonic device has speed and efficiency to serve optical computers

Researchers have developed an ultrafast light-emitting device that can flip on and off 90 billion times a second and could form the basis of optical computing.

Im Focus: Unlocking the rice immune system

Joint BioEnergy Institute study identifies bacterial protein that is key to protecting rice against bacterial blight

A bacterial signal that when recognized by rice plants enables the plants to resist a devastating blight disease has been identified by a multi-national team...

Im Focus: Smarter window materials can control light and energy

Researchers in the Cockrell School of Engineering at The University of Texas at Austin are one step closer to delivering smart windows with a new level of energy efficiency, engineering materials that allow windows to reveal light without transferring heat and, conversely, to block light while allowing heat transmission, as described in two new research papers.

By allowing indoor occupants to more precisely control the energy and sunlight passing through a window, the new materials could significantly reduce costs for...

Im Focus: Simulations lead to design of near-frictionless material

Argonne scientists used Mira to identify and improve a new mechanism for eliminating friction, which fed into the development of a hybrid material that exhibited superlubricity at the macroscale for the first time. Argonne Leadership Computing Facility (ALCF) researchers helped enable the groundbreaking simulations by overcoming a performance bottleneck that doubled the speed of the team's code.

While reviewing the simulation results of a promising new lubricant material, Argonne researcher Sanket Deshmukh stumbled upon a phenomenon that had never been...

Im Focus: NASA satellite camera provides 'EPIC' view of Earth

A NASA camera on the Deep Space Climate Observatory (DSCOVR) satellite has returned its first view of the entire sunlit side of Earth from one million miles away.

The color images of Earth from NASA's Earth Polychromatic Imaging Camera (EPIC) are generated by combining three separate images to create a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Euro Bio-inspired - International Conference and Exhibition on Bio-inspired Materials

23.07.2015 | Event News

Clash of Realities – International Conference on the Art, Technology and Theory of Digital Games

10.07.2015 | Event News

World Conference on Regenerative Medicine in Leipzig: Last chance to submit abstracts until 2 July

25.06.2015 | Event News

 
Latest News

Possible Path Toward First Anti-MERS Drugs

28.07.2015 | Life Sciences

Smart Hydrogel Coating Creates “Stick-slip” Control of Capillary Action

28.07.2015 | Materials Sciences

Are Fish Getting High on Cocaine?

28.07.2015 | Ecology, The Environment and Conservation

VideoLinks
B2B-VideoLinks
More VideoLinks >>>