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Autoimmune response can induce pancreatic tumor rejection
September 09, 2009PHILADELPHIA - Immune responses are capable of killing tumors before they can be directed toward normal body tissue, according to new scientific findings published in Cancer Research, a journal of the American Association for Cancer Research.
"There are extremely precise mechanistic methods augmenting the ability of the immune system to distinguish between normal tissues and tumors," said lead researcher Richard G. Vile, Ph.D. "Understanding the multiple checks and safeguards against autoimmunity should allow us to understand more closely how to generate antitumor immunity."
Vile, professor of immunology in the Department of Molecular Medicine and the Department of Immunology at the Mayo Clinic, Rochester, Minn., and professor of biological therapy at the University of Leeds, United Kingdom, along with other colleagues, induced pathological damage to a normal organ, in this case the pancreas, with the immune adjuvant hsp70. They investigated whether that damage could lead to the development of T-cell responses against the normal pancreas.
Inflammatory killing of the normal pancreas induced a Th-1-like, anti-self response to pancreatic antigens. Rapid suppression and damage to the pancreas induced a very strong suppressive regulatory T-cell response - Treg. Even after Treg cells were depleted, Vile and colleagues found that Th-1-like response was insufficient to induce significant ongoing autoimmunity.
"We believe that although there are additional mechanisms that prevent autoimmunity, simply removing the Treg uncovered a good antitumor response," Vile said. "We were not expecting that it would be possible to cure tumors without autoimmunity. Our prediction was that we would have to generate potent autoimmunity and then the tumors would be rejected."
Based on this study, the researchers suggested that it is more difficult than presumed to induce autoimmunity against the pancreas because multiple immune safeguards exist to prevent potentially autoimmune T-cells from destroying the normal pancreas. Further, when comparing the immunoprotective mechanisms of different tissues, profound differences exist in response to pathogen-like damage.
Cancer Research editorial board member Ivan Borrello, M.D., believes this study highlights several unique aspects of tumor immunology. The immune response toward normal elements and tumors in different organs are mediated through different mechanisms and may require different approaches to achieve a beneficial therapeutic outcome, he said. Further, in certain situations like the pancreas, it may not be sufficient to prime effective anti-tumor immunity.
"This study demonstrates the increasing complexity within which both normal tissues and tumors can protect themselves against destruction and underscores the complex network regulating immune responsiveness," said Borrello, an associate professor in oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.
These findings may lead to a new approach for the development of a cancer vaccination, Vile said, whereby scientists link the autoimmune and antitumor fields more closely than ever before.
Additional research is underway to evaluate this approach for the treatment of melanoma, as opposed to pancreatic cancer, and further studies are ongoing in prostate cancer. The field also needs to understand how to utilize and possibly sequence immune-mediated interventions in a more disease-focused and tailored manner, according to Borrello.
American Association for Cancer Research
Inflammatory killing of the normal pancreas induced a Th-1-like, anti-self response to pancreatic antigens. Rapid suppression and damage to the pancreas induced a very strong suppressive regulatory T-cell response - Treg. Even after Treg cells were depleted, Vile and colleagues found that Th-1-like response was insufficient to induce significant ongoing autoimmunity.
"We believe that although there are additional mechanisms that prevent autoimmunity, simply removing the Treg uncovered a good antitumor response," Vile said. "We were not expecting that it would be possible to cure tumors without autoimmunity. Our prediction was that we would have to generate potent autoimmunity and then the tumors would be rejected."
Based on this study, the researchers suggested that it is more difficult than presumed to induce autoimmunity against the pancreas because multiple immune safeguards exist to prevent potentially autoimmune T-cells from destroying the normal pancreas. Further, when comparing the immunoprotective mechanisms of different tissues, profound differences exist in response to pathogen-like damage.
Cancer Research editorial board member Ivan Borrello, M.D., believes this study highlights several unique aspects of tumor immunology. The immune response toward normal elements and tumors in different organs are mediated through different mechanisms and may require different approaches to achieve a beneficial therapeutic outcome, he said. Further, in certain situations like the pancreas, it may not be sufficient to prime effective anti-tumor immunity.
"This study demonstrates the increasing complexity within which both normal tissues and tumors can protect themselves against destruction and underscores the complex network regulating immune responsiveness," said Borrello, an associate professor in oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.
These findings may lead to a new approach for the development of a cancer vaccination, Vile said, whereby scientists link the autoimmune and antitumor fields more closely than ever before.
Additional research is underway to evaluate this approach for the treatment of melanoma, as opposed to pancreatic cancer, and further studies are ongoing in prostate cancer. The field also needs to understand how to utilize and possibly sequence immune-mediated interventions in a more disease-focused and tailored manner, according to Borrello.
American Association for Cancer Research
Autoimmune Response Current Events and Autoimmune Response News RSSNew link found between osteoporosis and coeliac disease
People with coeliac disease may develop osteoporosis because their immune system attacks their bone tissue, a new study has shown.
UM scientists pinpoint critical molecule to celiac disease, possibly other autoimmune disorders
It was nine years ago that University of Maryland School of Medicine researchers discovered that a mysterious human protein called zonulin played a critical role in celiac disease and other autoimmune disorders, such as multiple sclerosis and diabetes.
Device Protects Transplanted Pancreatic Cells from the Immune System
Scientists at Burnham Institute for Medical Research (Burnham) and the University of California San Diego (UC San Diego) School of Medicine have demonstrated in mice that transplanted pancreatic precursor cells are protected from the immune system when encapsulated in polytetrafluorethylene (PTFE).
MDC researchers prevent virus induced myocarditis
Life-threatening cardiac arrhythmia can be a consequence of myocarditis - an inflammation of the cardiac muscle that can be caused by the Coxsackievirus.
Don't be a stranger to yourself
One of the most important tasks of the immune system is to identify what is foreign and what is self. If this distinction fails, then the body's own structures will be attacked, the result of which could be an autoimmune disease such as diabetes mellitus type 1 or multiple sclerosis.
UCSF finds potential new antibody treatment for autoimmune diseases
Scientists at UCSF have discovered an abnormality in a patient's immune system that may lead to safer therapies for autoimmune diseases such as rheumatoid arthritis and colitis, as well as potential new ways to treat transplant rejection.
New scientific knowledge on juvenile diabetes
Finnish scientists have reported a breakthrough in the attempts to understand the development of type 1 diabetes. They discovered disturbances in lipid and amino acid metabolism in children who later progressed to type 1 diabetes, also known as juvenile diabetes.
Wistar researchers invigorate 'exhausted' immune cells
In battles against chronic infections, the body's key immune cells often become exhausted and ineffective. Researchers at The Wistar Institute have found a way to restore vigor to these killer T cells by blocking a key receptor on their surface, findings that may advance the development of new therapies for diseases such as HIV, hepatitis B and C, and cancer.
Accumulated bits of a cell's own DNA can trigger autoimmune disease
A security system wired within every cell to detect the presence of rogue viral DNA can sometimes go awry, triggering an autoimmune response to single-stranded bits of the cell's own DNA, according to a report in the August 22nd issue of the journal Cell, a Cell Press publication.
Study Underway to Find an Alternative Cure for Crohn's Disease and Ulcerative Colitis
Two research studies evaluating dietary changes and complementary medicine for the treatment of inflammatory bowel diseases (IBD) have been launched at Rush University Medical Center.
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