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 Custom-tailored strategy against glioblastomas
26.09.2016 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New leukemia treatment offers hope
23.09.2016 | King Abdullah University of Science and Technology

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: New welding process joins dissimilar sheets better

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of light metals.
Scientists at the University of Stuttgart have now developed two new process variants that will considerably expand the areas of application for friction stir welding.
Technologie-Lizenz-Büro (TLB) GmbH supports the University of Stuttgart in patenting and marketing its innovations.

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of...

Im Focus: First quantum photonic circuit with electrically driven light source

Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.

Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

HLF: From an experiment to an establishment

29.09.2016 | Event News

European Health Forum Gastein 2016 kicks off today

28.09.2016 | Event News

Laser use for neurosurgery and biofabrication - LaserForum 2016 focuses on medical technology

27.09.2016 | Event News

 
Latest News

New Multiferroic Materials from Building Blocks

29.09.2016 | Materials Sciences

Silicon Fluorescent Material Developed Enabling Observations under a Bright “Biological Optical Window”

29.09.2016 | Materials Sciences

X-shape Bio-inspired Structures

29.09.2016 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>