P02.02 * PRELIMINARY CHARACTERIZATION OF THE IMMUNE RESPONSE IN GLIOBLASTOMA BEFORE AND AFTER FIRST-LINE THERAPY

Abstract

BACKGROUND:Glioblastoma constitutes the mostcommon primary malignant brain tumor in adults. Its aggressive disease course is mediated by a hitherto poorly understood interplay of rapid tumor progression and therapy-related effects. Crucial factors include - amongst hypoxia, angiogenesis, and others - animmune response upfront and/or as aconsequence to combined chemo-radiotherapy. Herein, we aim at a systematic morphological characterization of this immune response based on a homogenous series of paired pre- and posttherapeutic glioblastoma samples. PATIENTS AND METHODS: A total of 15 glioblastoma patients newly diagnosed from 2005-2010 at the Medical University of Vienna were included in the analysis. All patients underwent neursurgical resection followed by standard radio- and TMZ-chemotherapy. At time of tumor recurrence second surgery was performed in all cases. Information on clinical characteristics and last follow-up were available. The tumor-associated immune response was semiquantitatively assessed using immunohistochemistry for anti-HLA-DR, CD3, and CD8. In addition, tumor-associated eosinophilia was assessed on conventional HE stains. RESULTS: Median age at diagnosis was 54 ys (range 21-69 ys). Median time from first to second surgery was 12.0 mths (range 1-26 mths) and median overall survival was 46.0 mths of the total cohort. While tumor-infiltrating CD3+ and CD8+ T-lymphocytes did not show a significant difference between first and second surgery (p = 0.07 and p = 0.3, respectively), a significant increase of HLA-DR+ microglia/macrophages (p = 0.01) was observed at time of tumor recurrence in the majority of cases (10/15; 66.7%). No unequivocal differences in overall survival were observed for those patients with enhanced microglial/macrophage response at time of tumor recurrence (log rank test; p = 0.34). A single case showed massive infiltration of eosinophils at second surgery only. This case differed from others by young age at diagnosis (26 ys), positive IDH-1 mutational and MGMT methylation status, short time to second surgery (1 mth) and exceptional favorable overall survival with stable disease at 84 mths. No peripheral eosinophilia or prior history of atopic disease was noted. Further screening for anti-neuronal/glial antibodies on a tissue-based assay did not yield a positive result. CONCLUSION: Although the small sample size implies cautious interpretation, we observed a significant increase of tumor-infiltrating microglia/macrophages in glioblastoma samples obtained after first-line therapy, while no significant differences were observed for tumor-infiltrating CD3+ and CD8+ T-lymphocytes. Of note, a single patient showed prominent tumor-associated eosinophilia upon second surgery which was associated with long-term survival.