Glioblastomas are the most common primary brain tumors. Surgery, radiation and chemotherapy improve survival but, unfortunately, these tumors remain deadly despite aggressive treatment. More-effective therapies are urgently needed. Reflecting his role as a neurosurgeon and clinician-scientist, the research group of Ian F. Parney, M.D., Ph.D., focuses on three main themes.
- Improving glioma surgery. Dr. Parney's lab seeks to develop and rigorously test techniques facilitating aggressive surgical resection for gliomas while maintaining or improving patient safety. These techniques include integrating functional imaging, including functional MRI and diffusion tensor imaging tractography, into image-guidance systems and intraoperative MRI. Then correlating this with intraoperative electrophysiological mapping and pursuing novel strategies such as fluorescence-guided resection.
- Understanding glioblastoma immunology. Glioblastomas suppress immune responses, both locally within the tumors and systemically throughout the body. Dr. Parney's team seeks to understand the cellular and molecular mechanisms underlying this immune suppression. They are testing the general hypothesis that a tightly regulated cellular network made up of glioblastoma cells, glioblastoma-infiltrating monocytes, circulating myeloid-derived suppressor cells and regulatory T cells underlies glioblastoma-mediated immunosuppression. The roles of immunosuppressive factors expressed by many of these cells, such as B7-H1, TGF-ß, PGE2 and IL-10, are being investigated. Model systems include in vitro interactions between cultured human glioblastoma cells, including glioma stem cells and human leukocytes. Other systems incorporated are humanized severe combined immunodeficient (SCID) and non-obese diabetic (NOD) mouse models reconstituted with human hematopoietic stem cells and bearing human glioblastoma stem cell xenografts. As much as possible, experiments are carried out with tumor cells and leukocytes obtained from patients undergoing glioblastoma surgery at Mayo Clinic, highlighting the translational nature of these studies.
- Developing effective glioblastoma immunotherapies. Based on an increased understanding of glioblastoma immunology, Dr. Parney's lab seeks to develop effective strategies to reverse glioblastoma-mediated immune suppression and stimulate anti-tumor immune responses. His team is particularly interested in optimizing tumor vaccine timing compared with standard therapies, which can alter glioblastoma-mediated immunosuppression. Manipulating dendritic cell vaccines to maximize their immunostimulatory properties and targeting critical cell populations, such as glioblastoma stem cells, are under investigation. In addition to studies carried out with the in vitro and in vivo model systems described above, Dr. Parney's team is fortunate to have access to the Mayo Clinic Human Cellular Therapy Laboratories. This good manufacturing practices (GMP) facility can produce clinical-grade cellular tumor vaccines. This collaboration enables Dr. Parney to readily translate his laboratory findings back to the clinic.
Significance to patient care
Dr. Parney's team is encouraged by the results the lab's research is producing, but also sobered by the fact that glioblastomas remain challenging tumors to address clinically. By pursuing these studies, his group hopes to improve the prognosis for patients facing this daunting diagnosis.