Dana-Farber Cancer Institute scientists have identified a protein that prevents the body's immune system from recognizing and attacking Hodgkin lymphoma cells. Based on this finding, the researchers are now investigating targeted therapies to disable this molecular "bodyguard" and boost a patient's ability to fight the blood cancer.
If the strategy proves successful, patients might escape some of the long-term complications -- like heart damage and the threat of a second cancer -- caused by standard treatments that include radiation, said Margaret Shipp, MD, of Dana-Farber, who headed the study. A report will be posted online by the Proceedings of the National Academy of Sciences on July 30 and will appear in an upcoming print issue of the journal.
"We're excited about this treatment lead," said Shipp, a medical oncologist. "We are currently generating antibodies that can neutralize the 'bodyguard' protein, and we’d like to fast-track this experimental therapy into clinical trials."
Nearly 8,200 people in the United States -- the great majority of them young adults -- will be diagnosed with Hodgkin lymphoma in 2007, according to the American Cancer Society, with an estimated 1,070 deaths. The cancer begins in the lymph nodes and channels that distribute infection-fighting white blood cells around the body. Its symptoms can include swollen glands in the neck, night sweats and fatigue.
The biological trademark of Hodgkin lymphoma is a type of giant, mutant white blood cell called the Reed-Sternberg cell that is found in the lymph node tumors. While most solid cancers consist almost entirely of tumor cells, says Shipp, Hodgkin tumors, which can reach the size of a basketball, contain only about 5 percent cancerous Reed-Sternberg cells; the rest are different types of immune cells recruited to fight the tumor, but they are ineffective.
"You would expect with all these host immune cells attracted to the area of the tumor cells that they would mount a great antitumor response," Shipp says. "But that's not the case. There are a lot of immune cells, but they're the wrong kind."
The immune army includes different types of T cells, such as T helper 1 (Th1) cells designed to recognize and kill foreign infectious agents and sometimes tumors, T helper 2 (Th2) cells, which normally control allergic responses, and T regulatory (Treg) cells that suppress other T-cell types and shut down an immune response when the job is done. The Hodgkin tumors are overloaded with Th2 and Treg cells that act as bodyguards for the cancer by weakening the Th1 immune response against it.
Przemyslaw Juszczynski, MD, PhD, Jing Ouyang, PhD, and colleagues from the Shipp laboratory, together with collaborators from Brigham and Women's Hospital, the Broad Institute and the University of Buenos Aires, hunted for the source of the cancer cells' protection. Using gene microarray chips, the scientists looked for genes that were active in Reed-Sternberg cells but not in cells of another non-Hodgkin B-cell lymphoma.
The comparison revealed that a gene called Gal1 was up to 30 times more active in the Reed-Sternberg cells, causing them to secrete large quantities of a protein -- Gal1 or Galectin 1 -- that turns down the Th1 immune response. The Shipp team then defined the mechanism for Gal1 overexpression in Hodgkin lymphoma. Next, they demonstrated that Th1 immune cells underwent apoptosis, or cell death, when treated with Gal1, leaving increased numbers of Th2 cells and the suppressive Treg cells. Using a gene-silencing technique, RNA interference or RNAi, they then turned off the Gal1 gene in Hodgkin Reed-Sternberg cells and showed that it blocked the death of infiltrating normal Th1 cells, making them an equal force to the Th2 cells.
"Likely what's happening here is that the tumor cells essentially hijack a normal regulatory program and use it to avoid being knocked off by the immune response," explains Shipp, who is also a professor of medicine at Harvard Medical School. "These observations provide an important explanation for why you have this ineffective immune response in Hodgkin lymphoma."
She adds that this bodyguard strategy may not be limited to Hodgkin lymphoma. One of the collaborating authors, Gabriel Rabinovich, PhD, of the University of Buenos Aires, has blocked Gal1 in mice with a form of the deadly skin cancer melanoma, and the animal's immune system succeeded in eliminating the cancer, Shipp says. "We think it's very possible that this strategy will be applicable to other types of cancer."
Bill Schaller | EurekAlert!
Hot cars can hit deadly temperatures in as little as one hour
24.05.2018 | Arizona State University
3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg
The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.
Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
25.05.2018 | Event News
02.05.2018 | Event News
13.04.2018 | Event News
25.05.2018 | Event News
25.05.2018 | Machine Engineering
25.05.2018 | Life Sciences