SCIDOT-34. BRAIN INJURY SIGNALS SYSTEMIC IMMUNOSUPPRESSION THROUGH THYMIC INVOLUTION. (11th November 2019)

• Record Type: Journal Article
• Authors: Ayasoufi, Katayoun; K Pfaller, Christian; H Khadka, Roman; Jin, Fang; Zheng, Jiaying; R Schuelke, Matthew; Evgin, Laura; J Hansen, Michael; T Himes, Benjamin; E Fain, Cori; P Tritz, Zachariah; N Goddery, Emma; T Yokanovich, Lila; R Pease, Larry; G Vile, Richard; J Johnson, Aaron
• Is Part Of: Neuro-oncology. Volume 21(2019)Supplement 6
• Page Start: vi278
• Page End: vi279
• Publication Date: 2019-11-11
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noz175.1170
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Systemic immunosuppression following neurological insults including stroke, traumatic brain injury, and glioblastoma (GBM) causes mortality and leads to failure of immune-modulating therapies. Exact immunological nature and the underlying mechanisms of this immunosuppression are unknown. Our goal was to define effects of neurological insults given exclusively to the brain on the thymus. The thymus is the primary immune organ responsible for T-cell development and maintenance both in children and in adults. We evaluated the brain-thymus communication using the following neurological insults: physical injury, CNS viral infection, sterile injury, tumor implantation, and seizures. All insults resulted in significant thymic involution that was reversible upon clearance of the insult. Thymic involution did not occur following similar peripheral insults. We next demonstrated that the GL261 model of GBM recapitulates hallmark features of peripheral immunosuppression observed in GBM patients including low CD4 T-cell counts. Thus, we aimed to further study the immunosuppression affecting the thymus in this clinically relevant model. Principle component analysis following RNA-sequencing of thymi from naïve and glioma-bearing mice revealed unbiased separation of the groups suggesting that the thymus is directly affected by a brain tumor. To determine the extent to which thymic involution was caused by a soluble factor we employed parabiosis. We demonstrated that thymic involution was transferable from glioma-bearing to non-tumor-bearing parabionts. Similarly, serum taken from GL261 glioma-bearing mice potently inhibited proliferation of T-cells in vitro . Together our data demonstrate that CNS-specific insults, regardless of nature, cause immunosuppression by prompting thymic involution through circulating factors. This accounts at least partially for immune deficiencies observed following neurological injuries. Identification of this suppressive factor is crucial in designing future therapeutics for GBM patients, and patients with other acute and chronic neurological trauma.