Navigation Links
Cancer stem cells suppress immune response against brain tumor
Date:1/15/2010

HOUSTON - Cancer-initiating cells that launch glioblastoma multiforme, the most lethal type of brain tumor, also suppress an immune system attack on the disease, scientists from The University of Texas M. D. Anderson Cancer Center report in a paper featured on the cover of the Jan. 15 issue of Clinical Cancer Research.

The researchers demonstrate that this subset of tumor cells, also known as cancer stem cells, stifles the immune response in a variety of ways, but that the effect can be greatly diminished by encouraging the stem cells to differentiate into other types of brain cell.

"We've known for years that glioblastoma and cancer patients in general have impaired immune responses," said senior author Amy Heimberger, M.D., an associate professor in M. D. Anderson's Department of Neurosurgery. "Our research uncovers an important mechanism that shows how that happens. The cancer stem cells inhibit T cell response, and it is these T cells that recognize and eradicate cancer."

Definitions of cancer stem cells vary. To meet the researchers' definition, the cells had to express a marker called CD133, form neurospheres (little round balls) in culture, and be able to recreate glioblastoma multiforme when injected into the brain of a mouse. They also had to be capable of differentiating into specific types of brain cells - neurons, astrocytes and glial cells.

Glioblastoma stem cells have been implicated in tumor resistance to chemotherapy and radiation, and are the believed to be responsible for the relentless recurrence of the disease, said first author Jun Wei, Ph.D., an instructor in the Department of Neurosurgery.

Wei explained that the glioblastoma stem cells suppress T cell response three different ways by:

  • Producing immunosuppressive cytokines that prevent the responses of T cells.
  • Inducing some T cells to become regulatory T cells, which act as brakes on the immune response.
  • Killing T cells via apoptosis, or programmed cell suicide. This is accomplished via the immunosuppressive protein B7-H1 in the stem cells directly contacting the T cells or by secretion of Galectin-3.

Wei said this immunosuppressive effect was reversed when the team placed the undifferentiated glioma stem cells in a culture medium that causes them to differentiate into the three types of neural cell.

"There are multiple research groups around the country, including ours, trying to develop vaccines or other immunotherapeutics against glioma stem cells," Heimberger said. "Now we have to be cognizant that the stem cell may deliver a fatal blow back to the immune system, which will help us understand how to design immune-based therapies."

New drugs or combination therapies are needed, because after decades of research, little progress has been made in treating glioblastoma multiforme. With the best of care patients survive an average of 14 months.

STAT3 pathway inhibits T cell response

In a separate paper in the Jan. 15 issue of Molecular Cancer Therapeutics, the research team also reports that the STAT3 signaling pathway is highly active in glioblastoma stem cells and suppresses immune system response.

Heimberger said the STAT3 molecule is known to induce cancer proliferation and survival migration and invasion, growth of new blood vessels, and immunosuppression.

Inhibiting STAT3, either by silencing it with small interfering RNA or by treatment with an experimental drug called WP1066, reactivates the immune response.

"We showed that if you treat the cancer stem cells with an inhibitor of STAT3, you can restore T cell proliferation and the ability of those cells to make pro-inflammatory cytokines," Heimberger said.

While the response is powerful it is not complete, so the researchers conclude there a STAT3-independent pathway is also at work in mediating immune suppression.

Research continues on how the inhibitors work, and whether they cause the stem cell differentiation that the team has shown reverses immune suppression.

The experimental drug WP1066 was developed by Waldemar Priebe, Ph.D., professor in M. D. Anderson's Department of Experimental Therapeutics. The drug has been shown to inhibit STAT3 in mice and reverse the immune suppression caused by cancer stem cells.


'/>"/>

Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

Related medicine news :

1. Gene Linked to Schizophrenia May Reduce Cancer Risk
2. Florida Brain Tumor Association & Moffitt Cancer Center Presents: The Bridge to Hope
3. Incorrect Cell Lines Used for Worldwide Cancer Research
4. Statewide Outreach & Information Service Program Operated by Northern California Cancer Center to End
5. Three Pioneering Ideas in Cancer Research Granted Prestigious Damon Runyon-Rachleff Innovation Awards
6. Lung cancer conference leaders honor Paul A. Bunn Jr., M.D.
7. Abbott Receives European Regulatory Approval for New Ovarian Cancer Diagnostic Test
8. The first map of colon cancer in Spain is published
9. Stress on Cells Can Turn Them Cancerous
10. Capital BlueCross and P4 Healthcare Launch Cancer Pathways Initiative
11. Therapy May Relieve Breast Cancer Surgery Complication
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Cancer stem cells suppress immune response against brain tumor
(Date:6/26/2016)... ... June 26, 2016 , ... PawPaws brand pet supplements owned by ... to enhance the health of felines. The formula is all-natural and is made from ... the PawPaws Cat Kidney Support Supplement Soft Chews are Astragalus Root Extract ...
(Date:6/25/2016)... ... ... Austin residents seeking Mohs surgery services, can now turn to Dr. Jessica ... Peckham for medical and surgical dermatology. , Dr. Dorsey brings specialization to include Mohs ... Mohs Micrographic Surgery completed by Dr. Dorsey was under the direction of Glenn Goldstein, ...
(Date:6/25/2016)... ... , ... As a lifelong Southern Californian, Dr. Omkar Marathe earned his Bachelors ... Geffen School of Medicine at UCLA. He trained in Internal Medicine at Scripps Green ... hematology/oncology at the UCLA-Olive View-Cedars Sinai program where he had the opportunity to train ...
(Date:6/24/2016)... ... June 24, 2016 , ... A recent article ... are unfamiliar with. The article goes on to state that individuals are now more ... these less common operations such as calf and cheek reduction. The Los Angeles area ...
(Date:6/24/2016)... ... June 24, 2016 , ... ... Scientific Sessions in Dallas that it will receive two significant new grants to ... came as PHA marked its 25th anniversary by recognizing patients, medical professionals and ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... OAKLAND, N.J. , June 24, 2016 /PRNewswire/ ... in the design, development and manufacturing of collagen ... and regeneration announced today that Bill Messer ... Sales and Marketing to further leverage the growing ... surgery medical devices. Bill joins the ...
(Date:6/24/2016)... June 24, 2016   Bay Area Lyme ... Dean Center for Tick Borne Illness , ... Rehabilitation, MIT Hacking Medicine, University of California, Berkeley, ... announced the five finalists of Lyme Innovation ... More than 100 scientists, clinicians, researchers, entrepreneurs, and ...
(Date:6/24/2016)... 2016 Research and Markets ... Electronics 2015-2025: Applications, Technologies, Forecasts" report to ... In-Mold Electronics, Smart Skin, Structural Health Monitoring, Composite ... Structural electronics involves electronic and/or electrical components and ... dumb structures such as vehicle bodies or conformally ...
Breaking Medicine Technology: