Rice University study yields new two-step strategy for weakening cancer
Research by Rice University scientists who are fighting a cyberwar against cancer finds that the immune system may be a clinician's most powerful ally.
"Recent research has found that cancer is already adept at using cyberwarfare against the immune system, and we studied the interplay between cancer and the immune system to see how we might turn the tables on cancer," said Rice University's Eshel Ben-Jacob, co-author of a new study this week in the Early Edition of the Proceedings of the National Academy of Sciences.
Ben-Jacob and colleagues at Rice's Center for Theoretical Biological Physics (CTBP) and the University of Texas MD Anderson Cancer Center, developed a computer program that modeled a specific channel of cell-to-cell communication involving exosomes. Exosomes are tiny packets of proteins, messenger RNA and other information-coding segments that both cancer and immune cells make and use to send information to other cells.
"Basically, exosomes are small cassettes of information that are packed and sealed inside small nanoscale vesicles," Ben-Jacob said. "These nanocarriers are addressed with special markers so they can be delivered to specific types of cells, and they contain a good deal of specific information in the form of signaling proteins, snippets of RNA, microRNAs and other data. Once taken by the target cells, these nanocarriers can order cells to change what they are doing and in some cases even change their identity."
Ben-Jacob said recent research showed that dendritic cells use exosomal communications to carry out their specialized role as moderators of and mediators between the innate and adaptive immune systems. The innate and adaptive immune systems use different strategies to protect the body from disease.
The innate system guards against all threats at all times and is the first to act even against unrecognized invaders. In contrast, the adaptive immune system acts more efficiently, and in a specific way, against recognized, established threats. Dendritic cells, which are part of both the innate and adaptive systems, share information and help "coach" the adaptive system's hunter-killer cells about which cells to target and how best to destroy them.
"We were inspired to do this research by two papers -- one that showed how the dendritic cells use the exosome to fight cancer and another that showed how cancer cells co-opt the exosomal system both to prevent the bone marrow from making dendritic cells and disable dendritic cells' coaching abilities," Ben-Jacob said. "This is cyberwarfare, pure and simple. Cancer uses the immune systems' own communications network to attack not the soldiers but the generals that are coordinating the body's defense."
To examine the role of exosome-mediated cell-to-cell communication in the battle between cancer in the immune system, Ben-Jacob and postdoctoral fellow Mingyang Lu, the study's first author, worked with CTBP colleagues to create a computer model that captured the special aspects of the exosomal exchange between cancer cells, dendritic cells and the other cells in the immune system.
"You should imagine there is a tug-of-war between the cancer and the immune system," said study co-author and CTBP co-director José Onuchic, Rice's Harry C. and Olga K. Wiess Professor of Physics and Astronomy. "Sometimes one side wins and sometimes the other. The question is whether we can understand this battle enough to use radiotherapy or chemotherapy in such a way as to change the balance of the tug-of-war in favor of the immune system."
Based on their findings, Ben-Jacob and Onuchic say the answer is likely yes. In particular, the CTBP model found that the presence of exosomes creates a situation where three possible cancer states can exist, and one of the states -- an intermediate state in which cancer is neither strong nor weak but the immune system is on high alert -- could be the key for a new therapeutic approach and with reduced side effects.
"When exosomes are not included, there are only two possible states -- one where cancer is strong and the immune system is weak and the other where cancer is weak and the immune system is strong," Ben-Jacob said.
Although the state where cancer is weakened is preferable, there is a growing body of clinical evidence that suggests it is very difficult to force cancer directly from the strong to the weak position, in part because radiation and chemotherapeutic treatments also weaken the immune system as they weaken cancer.
"It is fairly common that a cancer recedes following treatment only to return stronger than ever in just a few months or weeks," said study co-author Sam Hanash, professor of clinical cancer prevention and director of the Red and Charlene McCombs Institute for the Early Detection and Treatment of Cancer at MD Anderson. "The new model captures this dynamic and suggests alternative scenarios whereby the immune system does its job fighting the cancer."
Ben-Jacob said the team showed that it was possible to force cancer from the strong to the moderate state by alternating cycles of radiation or chemotherapy with immune-boosting treatments.
"Our model shows that just a few of these treatment-boosting cycles can alter the cancer-immune balance to help the immune system bring the cancer to the moderate state," Ben-Jacob said. "Once in the intermediate state, cancer can be brought further down to the weak state by a few short pulses of immune boosting.
"It is much more effective to use a two-step process and drive cancer from the strong to the intermediate state and then from the intermediate to the weak state," he said. "Without the exosome -- the cancer-immune cyberwar nanocarriers -- and the third state, this two-step approach wouldn't be possible."
Ben-Jacob is a senior investigator at CTBP, adjunct professor of biochemistry and cell biology at Rice and the Maguy-Glass Chair in Physics of Complex Systems and professor of physics and astronomy at Tel Aviv University.
In addition to Ben-Jacob, Onuchic and Lu, study co-authors include Rice graduate student Bin Huang and Sam Hanash, director of the Red and Charline McCombs Institute for the Early Detection and Treatment of Cancer at the University of Texas MD Anderson Cancer Center.
High-resolution IMAGES are available for download at:
CAPTION: A cancer cell under attack by lymphocytes.
CREDIT: thinkstockphotos.com/Rice University
CAPTION: "Dendritic Cell Revealed," an artist's rendering of the surface of a human dendritic cell.
CREDIT: National Institutes of Health (NIH)
CAPTION: Eshel Ben-Jacob
CREDIT: Tommy LaVergne/Rice University
A copy of the PNAS abstract is available at: http://www.pnas.org/content/early/2014/09/18/1416745111.abstract
This release can be found online at news.rice.edu.
Follow Rice News and Media Relations on Twitter @RiceUNews.
Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation's top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,920 undergraduates and 2,567 graduate students, Rice's undergraduate student-to-faculty ratio is just over 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is highly ranked for best quality of life by the Princeton Review and for best value among private universities by Kiplinger's Personal Finance.
David Ruth | Eurek Alert!
Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care
Disrupted fat breakdown in the brain makes mice dumb
19.05.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...
For the first time, scientists have succeeded in studying the strength of hydrogen bonds in a single molecule using an atomic force microscope. Researchers from the University of Basel’s Swiss Nanoscience Institute network have reported the results in the journal Science Advances.
Hydrogen is the most common element in the universe and is an integral part of almost all organic compounds. Molecules and sections of macromolecules are...
22.05.2017 | Event News
17.05.2017 | Event News
16.05.2017 | Event News
22.05.2017 | Materials Sciences
22.05.2017 | Life Sciences
22.05.2017 | Physics and Astronomy