Integration of epidemiology, immunobiology, and translational research for brain tumors.

Abstract

We recently identified a pivotal role for the host type I interferon (IFN) pathway in immunosurveillance against de novo mouse glioma development, especially through the regulation of immature myeloid cells (IMCs) in the glioma microenvironment. The present paper summarizes our published work in a number of areas. We have identified single-nucleotide polymorphisms (SNPs) in human IFN genes that dictate altered prognosis of patients with glioma. One of these SNPs (rs12553612) is located in the promoter of IFNA8 and influences its activity. Conversely, recent epidemiologic data show that chronic use of nonsteroidal anti-inflammatory drugs lowers the risk of glioma. We translated these findings back to our de novo glioma model and found that cyclooxygenase-2 inhibition enhances antiglioma immunosurveillance by reducing glioma-associated IMCs. Taken together, these findings suggest that alterations in myeloid cell function condition the brain for glioma development. Finally, in preliminary work, we have begun applying novel immunotherapeutic approaches to patients with low-grade glioma with the aim of preventing malignant transformation. Future research will hopefully better integrate epidemiological, immunobiological, and translational techniques to develop novel, preventive approaches for malignant gliomas.

• Authors: Hideho Okada, Michael E Scheurer, Saumendra N Sarkar, Melissa L Bondy
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1284 Pg. 17-23 (May 2013) ISSN: 1749-6632 [Electronic] United States
• PMID: 23651189 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 New York Academy of Sciences.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Interferon Type I
• Cyclooxygenase 2

Topics

• Allergy and Immunology
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Brain Neoplasms (epidemiology, immunology, pathology)
• Cyclooxygenase 2 (metabolism)
• Disease Models, Animal
• Glioma (epidemiology, immunology, metabolism, pathology)
• Humans
• Immunotherapy (methods)
• Inflammation
• Interferon Type I (immunology)
• Mice
• Myeloid Cells (cytology)
• Polymorphism, Single Nucleotide
• Risk Factors
• Translational Research, Biomedical