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Dr. Foreman's latest work TSF has supported |
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Foreman: R01 for immune research in ependymoma Dr. Nicholas Foreman (UCCC Developmental Therapeutics/SOM Pediatrics/The Children’s Hospital) has received a $1.2 million, four-year NCI R01 to continue groundbreaking work into his group’s discovery that immune gene and cell enrichment is associated with a good prognosis in ependymoma.About half of children diagnosed with ependymoma brain tumors recur after standard treatment—surgery and radiation—and most who recur will die, says Foreman, director of pediatric neuro-oncology at The Children’s Hospital. One in 11 pediatric brain tumors are ependymomas, with about 200 new cases of the disease in the United States each year. In the Nov. 16, 2009, issue of the Journal of Immunology, Foreman and colleagues showed that: Genes associated with nonrecurrent ependymoma were predominantly immune function-related. Increased expression of immune-related genes were correlated with longer time to progression in recurrent ependymoma. 95 percent of genes associated with both of these phenotypes associated with immune function, and a histological analysis of a gene subset showed their expression was restricted to a subpopulation of tumor-infiltrating cells—predominantly CD4 T cells in the nonrecurrent type.
“Immune Gene and Cell Enrichment Is Associated with a Good Prognosis in Ependymoma.” “As we looked closely at the tumor cells, we realized this immune expression wasn’t a function of the tumor, but of the immune cells which, in some cases, were in large quantities in the tumor,” says Foreman. “It turned out to be the first demonstration in any brain tumor that the immune status of the individual at diagnosis is directly related to his or her chance of being cured.”The researchers also found that certain aspects of the immune function could be blocking treatment’s effectiveness, which flies against common belief that all immune reactions to a tumor are positive. Foreman’s work is based on a human model of the immune system and outcomes. Most other experiments have been done in animal models. It also uses a new technique that uses tumor samples that are flash-frozen in the operating room. “We disrupt the tissue and then separate the cells using Flow Cytometry to study them in more detail,” he says. “At first, we weren’t sure this could be done on frozen cells, but we’ve proven it works well and allows us to look in detail at individual subcell populations, not only what cells they are but their activation states. We think this technique will finally allow us to detail the immune response.”Foreman, who is chair of the COG ependymoma committee, says none of this work would have been possible without support from the family of Tanner Seebaum, a patient who had recurrent ependymoma and survived. Tanner’s family helped found an endowed chair (held jointly at Children’s and the SOM) and the Seebaum Foundation also made direct gifts to support the research.Foreman’s Colorado collaborators are Dr. Andrew Donson, senior research associate in the Foreman lab, UCCC members Drs. Bette DeMasters (UCCC Immunology & Immunotherapy/SOM Pathology), Allen Waziri (UCCC Immunology & Immunotherapy/SOM Neurosurgery), and Michael Wang (Cancer Cell Biology/SOM Pediatrics); and Dr. Michael Handler, chief of pediatric neurosurgery at the SOM and Children’s.
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