Turning To The Immune System To Fight Malignant Glioma: UPCI Researchers Present Novel Findings At AACR Annual Meeting

Main Category: Cancer / Oncology
Article Date: 14 Apr 2008 - 11:00 PST

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Mitsugu Fujita, M.D., Ph.D., and Ryo Ueda, M.D., Ph.D., both researchers with the University of Pittsburgh Cancer Institute's (UPCI) Brain Tumor Program, are pursuing the same aim: understanding the body's immune system in order to fight the deadliest and most common form of brain cancer. At the American Association for Cancer Research (AACR) Annual Meeting, April 12 to 16, in San Diego, they will present research discussing their novel approaches to achieving this goal.

Dr. Fujita's poster, abstract number 261, entitled "CXCL10 produced by DC1 plays a pivotal role in inducing long-lasting type-1 CTLs that mediate an effective anti-brain tumor immune response," will be presented as part of the Immune Biology/Tumor Microenvironment Session.

"The most common form of primary brain tumors is malignant glioma, and currently no cure exists," explains Dr. Fujita. "Surgery and radiotherapy can be performed and chemotherapy can be administered, but this disease is like a death sentence. There is an urgent demand for further advanced, molecular-targeted therapies. Immunotherapy is believed to be one such novel strategy. In the research I'm presenting, we decided to investigate what happens when you use novel dendritic cells for glioma treatment, since we have found it is these cells that can control immune reaction most efficiently."

For this study, Dr. Fujita and his colleagues developed a novel protocol to generate mouse bone marrow-derived type-1 dendritic cells, or DCs, which were named DC1. These cells are capable of inducing type-1 cytotoxic T lymphocytes (CTL) - cells that can kill cancer cells and at the same time, escape from cancer cell attacks. These DC1 cells were allowed to fully mature, loaded with glioma-associated molecules, and then injected into glioma-bearing mice. Mice injected with DC1 cells had a prolonged survival compared to mice injected with standard DCs.

"Essentially, in our mouse models, we proved that there is a basis for further research into using DC1 cells, which, in theory, can be induced in glioma patients, to fight the cancerous cells," said Dr. Fujita. "If we can find a way for these cells to neutralize malignant glioma cells, we might be able to cure this disease."

Dr. Ueda will head a mini-symposium, discussing his research presentation "Dicer-regulated micro RNAs 222 and 339 promote immune-escape of cancer cells through down regulation of ICAM-1." According to Dr. Ueda, the RNase III endonuclease Dicer plays a key role in the generation of mature, 22-nucleotide-long micro RNAs (miRNAs) in cells. Recent studies suggest that Dicer is highly expressed in cancer and is involved in immune regulation.

"Based on these facts, we hypothesized that cancer cells which express Dicer might regulate their susceptibility against immune-surveillance through processing miRNAs," said Dr. Ueda.

Dr. Ueda also will present his research into identifying specific Dicer-regulated miRNAs that modulate expression of ICAM (say what this is), which is required for CTL-tumor cell interactions. Together, his results suggest that Dicer is responsible for creating the miRNAs which prevent CTL cells from "attacking" tumor cells, thwarting an immunologic response to malignant glioma cells.

"Inhibitory strategies against miRNAs which promote immune-escape of cancer cells will have a rationale for therapeutic applications for cancer in the future. At a basic science level, our research shows immense possibility in utilizing the immune system to fight malignant gliomas," said Dr. Ueda. "The challenge rests in taking this research from the laboratory and translating it into clinical trials for cancer patients. It's a challenge we are looking forward to tackling."

Founded in 1984, the University of Pittsburgh Cancer Institute became a National Cancer Institute-designated Comprehensive Cancer Center in record time (by 1990). UPCI, the only cancer center in western Pennsylvania with this elite designation, serves the region's population of more than 6 million. Presently, UPCI receives a total of $154 million in research grants, and is ranked 10th in funding from the National Cancer Institute (NCI).

http://www.upmc.edu