IMMU-70. GLOBAL IMMUNE FINGERPRINTING IN GLIOBLASTOMA REVEALS IMMUNE-SUPPRESSION SIGNATURES ASSOCIATED WITH PROGNOSIS. (5th November 2018)

• Record Type: Journal Article
• Authors: Alban, Tyler; Alvarado, Alvaro; Sorensen, Mia; Bayik, Defne; Volovetz, Josephine; Serbinowski, Emily; Mulkearns-Hubert, Erin; Sinyuk, Maksim; Hale, James; Onzi, Giovana; McGraw, Mary; Huang, Pengjing; Grabowski, Mathew; Wathen, Connor; Radivoyevitch, Tomas; Kornblum, Harley; Kristensen, Bjarne W; Vogelbaum, Michael; Lathia, Justin
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 6
• Page Start: vi137
• Page End: vi137
• Publication Date: 2018-11-05
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy148.573
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Therapeutic resistance in glioblastoma (GBM) is linked to cancer stem cells and signaling pathway alterations, but the role of local and systemic immune suppression during disease progression is less understood. To determine how the immune system as a whole is altered in GBM patients, a CyTOF panel of 25 immune markers was developed for immune fingerprinting of peripheral blood mononuclear cells (PBMCs). CyTOF analysis was performed on select patients with either favorable or poor prognosis from a cohort of newly diagnosed GBM patients, from whom PBMCs were collected throughout disease progression. Multi-dimensional cluster analysis identified a reduction of Monocytic Myeloid-Derived Suppressor Cells (M-MDSCs) in the patient with favorable prognosis, while the patient with poor prognosis had higher levels of M-MDSCs. Additionally, when LGG patients were compared to GBM patients, LGG patients had more Dendritic cells and Natural Killer cells as compared to GBM patients. To understand whether this elevation in MDSC was unique to GBM or whether MDSCs were high across primary and secondary brain tumors, a cohort of 259 patient PBMC samples was analyzed. GBM patients had a significant elevation in MDSCs in blood, but not immunosuppressive T regulatory cells as compared to non-malignant brain tumors. To determine whether MDSCs in the GBM microenvironment also correlate with survival, a cohort of patients with matched primary and secondary resections were analyzed for MDSCs by immunofluorescence, which determined that intra-tumoral MDSCs correlate with poor prognosis in recurrent samples, while general myeloid infiltration correlated with a good prognosis. These studies identify low MDSC immune signatures that are linked to enhanced pro-inflammatory cells and overlap between GBM patients with a good prognosis and LGG patients, promoting the idea of targeting MDSCs in GBM patients to alter their immune status to that of a lower grade tumor.