53 CHAPTER 5 MECHANISMS OF IMMUNE EVASION BY GLIOMAS Cleo E. Rolle, 1 Sadhak Sengupta 1 and Maciej S. Lesniak* ,2 1 Department of Surgery, Section of Neurosurgery, The University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA; 2 Section of Neurosurgery, The University of Chicago, Chicago, Illinois, USA *Corresponding Author: Maciej S. Lesniak—Email: mlesniak@surgery.bsd.uchicago.edu Abstract: A major contributing factor to glioma development and progression is its ability to evade the immune system. This chapter will explore the mechanisms utilized by glioma to mediate immunosuppression and immune evasion. These include intrinsic mechanisms linked to its location within the brain and interactions between glioma cells and immune cells. Lack of recruitment of naïve effector immune cells perhaps accounts for most of the immune suppression mediated by these tumor cells. This is enhanced by increased recruitment of microglia which resemble immature antigen presenting cells that are unable to support T-cell mediated immunity. Furthermore, secreted factors like TGF-, COX-2 and IL-10, altered costimulatory molecules and inhibition of STAT-3 all contribute to the recruitment and expansion of regulatory T cells, which further modulate the immunosuppressive environment of glioma. In light of these findings, multiple immunotherapeutic treatment modalities are currently being explored. INTRODUCTION The brain has classically been considered an immune privileged organ isolated from the immune system on the basis of several key observations. Seminal transplant immunology studies conducted by Medewar found that foreign tissues implanted in the brain were not immediately rejected. 1 Later work suggested that this was due to the fact that the brain was physical isolated from the immune system by the blood-brain barrier (BBB). Further, it was suggested that the brain was not connected to the lymphatic system and that lymphocytes did not traffic into the brain. However, with improvements in techniques and assessment of immune responses the concept of immune privilege was Glioma: Immunotherapeutic Approaches, edited by Ryuya Yamanaka. ©2012 Landes Bioscience and Springer Science+Business Media.