There is increasing interest in considering brain tumors as tissues with underlying morphological and molecular organization that can be approached in much the same way as, for example, the subventricular zone of mammalian brain. Towards this end, we have interrogated sections of primary human glioma for antigens relevant for immunotherapy targeting such as IL13Ralpha2 (expressed on tumor cells but not normal brain tissues), and for receptors and signaling molecules relevant to tumor biology (for example HER2, EGFR). Examination of large (centimeter)-scale highresolution (1 um/pixel) images provides evidence for variation in gene expression patterns associated with tumor structure (such as pseudopalisading necrosis) and suggestions of reciprocal spatial expression patterns for some of these antigens. This information will contribute to the design of more effective immunotherapies as well as to our understanding of glioma origins, progression and dissemination. IR-002. TESTING AND ANALYSIS OF FLUORESCENT MARKERS PANEL FOR T-CELLS' MULTIFUNCTIONALITY IN GLIOBLASTOMA MULTIFORME PATIENTS IR-003. CCR41 REGULATORY T CELLS ACCUMULATE WITHIN THE BRAIN TUMOR IN AN EXPERIMENTAL MODEL OF GBMAlan Chang, Derek Wainwright, Mahua Dey, Yu Han, and Maciej Lesniak; University of Chicago, Chicago, IL, USA Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. One hallmark of GBM is the accumulation of infiltrating regulatory T cells (Tregs), a highly immunosuppressive T cell subset that suppresses T cell-mediated GBM rejection. Previous work has demonstrated that the Treg-recruiting chemokine, CCL22, is expressed by patient-resected GBM. Importantly, the number of Tregs expressing CCR4, the cognate chemokine receptor for CCL22, is increased in the peripheral blood of GBM patients. To investigate the therapeutic potential of targeting the CCL22-CCR4 axis in brain tumors, we systematically-analyzed the level of CCR4-expressing Tregs as well as the mRNA expression level of CCL22 and an additional CCR4-specific chemokine, CCL17. Using the orthotopic GL261 cell-based model, we found a progressive accumulation of CCR4+ Tregs in the brain tumor. Coincidently, the expression of the Treg-recruiting chemokines, CCL17 and CCL22, was predominantly localized to the tumor-infiltrating leukocytes, rather than the tumor tissue itself. Interestingly, CCL17, but not CCL22, was also expressed by both tumor and non-tumor cells in the brain. These results implicate the chemokine receptor CCR4 as a therapeutic target for further investigation as a potential strategy to target Treg trafficking to GBM.

PURPOSE: This study was performed to evaluate the incidence of seizures with its implications on disease progression and the diagnostic value of post-ictal magnetic resonance images (MRI) during the management of highgrade gliomas (HGGs). PATIENTS AND METHODS: A total of 406 consecutive patients with newly diagnosed HGGs were retrospectively reviewed. The incidence of seizure attacks during the management was investigated. In patients who experienced a seizure, the causality between seizures and disease progression was assessed by pre-ictal, post-ictal (,1 month), and follow-up (,3 months) MRI. RESULTS: After a mean follow-up of 21.9 months (range, 0.1 -88.3), seizure attacks developed in 127 patients (31%). Of the 127 patients, radiological progression at the post-ictal MRI was found in 83 patients (65%) and the follow-up MRI confirmed progression in 79 patients (62%). However, other 4 patients (3%) were shown to be progression-free. Among those without radiological progression at the post-ictal MRI, the follow-up MRI confirmed progression-free in 31 patients (24%); however, 13 patients (10%) revealed eventual progression. In the patients with a seizure, absence of preoperative seizure (p ¼ 0.003), , 95% tumor resection (p ¼ 0.001), and pre-ictal Karnofski Performance Scale score ≤ 70 (p ¼ 0.025) were significantly associated with disease progression. CONCLUSION: During the management of HGG, 31% of patients experienced seizures; of these patients, 72% harbored progressive disease. The post-ictal MRI is useful for detecting disease progression; however, there are pitfalls. Clinical settings should be considered together for diagnosing disease progression in patients with seizures.