Jefferson scientists find protein helps pancreatic cancer cells evade immune system and spreadJanuary 11, 2008A protein that helps prevent a woman's body from rejecting a fetus may also play an important role in enabling pancreatic cancer cells to evade detection by the immune system, allowing them to spread in the body. Researchers at Jefferson's Kimmel Cancer Center in Philadelphia found that the metastatic cancer cells in the lymph nodes of patients with pancreatic cancer produce enough of the protein, IDO, to essentially wall-off the immune system's T-cells and recruit cells that suppress the immune system's response to the tumor. The findings might mean not only a better way to detect pancreatic cancer spreading to lymph nodes, but also could enhance tumor immune therapy strategies against the fast-moving, deadly disease. According to Jonathan Brody, Ph.D., assistant professor of Surgery at Jefferson Medical College of Thomas Jefferson University, one way that metastatic cancer cells can survive in nearby lymph nodes is by avoiding the immune system. Evidence from studies by scientists looking at other cancers has indicated that IDO (indolamine 2'3 dioxygenase) is critical to regulating the "immune environment." The Jefferson scientists wanted to know if metastatic pancreatic cancer cells residing in the lymph nodes expressed IDO to avoid being found, and if so, could they target this enzyme with available drugs to prevent the cancer cells from hiding from the immune system.
Dr. Brody, Charles Yeo, M.D., Samuel D. Gross Professor and chair of Surgery at Jefferson Medical College and their co-workers analyzed IDO expression in 14 lymph nodes to which pancreatic cancer cells had spread and compared them to the primary tumors that had not spread in the same patients. In every case, they found greater expression of the IDO protein in the cancerous lymph nodes. They also looked at three cases of lymph node-negative pancreatic cancers, finding little IDO present. Scientists know that IDO shuts off tryptophan production in T-cells, putting them in a resting state, and recruits a different type of immune cell called T-regulatory cells, which can inhibit the immune system. "If cells are escaping the primary tumor and going into another environment such as the lymph nodes, what are they doing to evade detection by the immune system?" says Dr. Brody. "These data point to the fact that IDO may play a role in helping cancer cells avoid the immune system." His team reported its findings at the recent meeting of the Southern Surgical Association in Hot Springs, VA. The results have been accepted for publication in the Journal of the American College of Surgeons. The group also examined pancreatic cancer cell lines in the laboratory for IDO expression. Using antibodies to IDO, they didn't find any IDO expression until they treated the cells with interferon to mimic the conditions in the lymph nodes. The tumor cells were then able to make the enzyme. Whether or not the cancer has spread to the lymph nodes can affect a patient's prognosis, particularly after surgery. While scientists know a great deal about how a pancreatic cancer develops from a pre-cancerous growth into a cancer, they still don't have a clear understanding of how it progresses from a primary cancer to metastatic disease. IDO, Dr. Brody says, may play an important part in the process. "The immune system appears to have a balance that can allow cancer cells to grow but also can detect and destroy them, Brody explains. "While IDO is crucial to regulating this balance, too much IDO tips the balance toward an immune suppression, supporting cancer growth." Dr. Brody notes that IDO inhibitors are available clinically, and these could in theory be used with chemotherapy or perhaps other forms of immune therapy against pancreatic cancer. An inhibitor might be able to activate T-cells to kill cancer cells, for example. "Presumably we could give IDO inhibitors up front to patients who we know are lymph node-positive to try to reduce the cancer and possibly convert them to surgical candidates," he explains. Pancreatic cancer, the fourth-leading cause of cancer death in this country, takes some 33,000 lives a year. The disease is difficult to treat, particularly because it is frequently detected after it has spread to other areas on the body. Only 5 percent of all individuals with pancreatic cancer live for five years after diagnosis, and approximately 25 percent of those diagnosed with pancreatic cancer who undergo successful surgical removal of their disease live at least that long. But recent figures give new hope: of those who live for five years after surgical resection, some 55 percent will be alive at least another five years. Thomas Jefferson University Science News and Science Current Events Tag Cloud This tag cloud is a visual representation of term frequencies of random science news topics with common terms grouped together and emphasized by their display size. Clostridium difficile Rheumatoid Arthritis Food Safety Smallpox Lead Exposure Skin Cancer Fusion Whales Anorexia Pheromone Glaciers Solar Energy Laser Cannabis Nanotechnology Neural Stem Cells Placebo Cancer Care Irrigation Sleep Deprivation Lupus Type 1 Diabetes Immune Cell Cesarean Sea Level
See More: Science News Tags | |||||||||||||||||||||
|
Related Pancreatic Cancer Current Events and Pancreatic Cancer News Articles Being overweight, obese during early adulthood associated with greater risk of pancreatic cancer Young adults who are overweight or obese have an increased risk of pancreatic cancer, and being obese at an older age is associated with a lower overall survival rate for patients with pancreatic cancer. M. D. Anderson study finds strong relationship between high body mass index, pancreatic cancer In reviewing the weight history of pancreatic cancer patients across their life spans, researchers at The University of Texas M. D. Anderson Cancer Center have determined that a high body mass index in early adulthood may play a significant role in an individual developing the disease at an earlier age. Adenoviral vector specifically targeted to EphA2 receptor in pancreatic cancer cells Pancreatic cancer is a devastating disease with poor prognosis. This warrants the development of novel therapies including gene therapy. Colon Cancer Screening Technique Shows Continued Promise in New Study Recent clinical trials show that a new colon cancer screening technique created by Northwestern University researchers has a high enough sensitivity that it could potentially be as or more successful than a colonoscopy in screening for colon cancer. Mayo Clinic finds new pathology tests double sensitivity to detect bile duct and pancreatic cancers Pancreatic cancer and bile duct cancer are difficult to diagnose and often fatal because they are discovered in the advanced stages of the disease. miR-196a promotes the metastases of tumors MicroRNAs are small RNA molecules of 20-25 nucleotides length, regulating gene expression by inhibition of transcription or translation of proteins. Popular diabetes treatment could trigger pancreatitis, pancreatic cancer A drug widely used to treat Type 2 diabetes may have unintended effects on the pancreas that could lead to a form of low-grade pancreatitis in some patients and a greater risk of pancreatic cancer in long-term users, UCLA researchers have found. Regulation of cell proliferation by the OGF-OGFr axis is dependent on nuclear localization signals Researchers at The Pennsylvania State University College of Medicine, Hershey, Pennsylvania have discovered that the efficacy of the Opioid Growth Factor (OGF, [Met5]-enkephalin), a clinically important antitumor agent, is dependent on nucleocytoplasmic translocation and reliant on the integrity of nuclear localization signals in the OGF receptor (OGFr). Newly discovered epidermal growth factor receptor active in human pancreatic cancers Finally some promising news about pancreatic cancer, one of the most fatal cancers, due to the difficulties of early detection and the lack of effective therapies: Johns Hopkins University pathologist Akhilesh Pandey has identified an epidermal growth factor receptor aberrantly active in approximately a third of the 250 human pancreatic cancers studied. New drug achieves pancreatic cancer tumor remission and prevents recurrence Pancreatic cancer remains one of the deadliest cancers, but researchers may have found a combination therapy to reduce cancer stem cells and stop pancreatic cancer growth. Results will be presented at the American Association for Cancer Research 100th Annual Meeting 2009. More Pancreatic Cancer Current Events and Pancreatic Cancer News Articles |
|||||||||||||||||||||
|
|||||||||||||||||||||
|
|||||||||||||||||||||