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SCIDOT-34. BRAIN INJURY SIGNALS SYSTEMIC IMMUNOSUPPRESSION THROUGH THYMIC INVOLUTION

Publication ,  Journal Article
Ayasoufi, K; K Pfaller, C; H Khadka, R; Jin, F; Zheng, J; R Schuelke, M; Evgin, L; J Hansen, M; T Himes, B; E Fain, C; P Tritz, Z; R Pease, L ...
Published in: Neuro-Oncology
November 11, 2019

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.

Duke Scholars

Published In

Neuro-Oncology

DOI

EISSN

1523-5866

ISSN

1522-8517

Publication Date

November 11, 2019

Volume

21

Issue

Supplement_6

Start / End Page

vi278 / vi279

Publisher

Oxford University Press (OUP)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1109 Neurosciences
 

Citation

APA
Chicago
ICMJE
MLA
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Ayasoufi, K., K Pfaller, C., H Khadka, R., Jin, F., Zheng, J., R Schuelke, M., … J Johnson, A. (2019). SCIDOT-34. BRAIN INJURY SIGNALS SYSTEMIC IMMUNOSUPPRESSION THROUGH THYMIC INVOLUTION. Neuro-Oncology, 21(Supplement_6), vi278–vi279. https://doi.org/10.1093/neuonc/noz175.1170
Ayasoufi, Katayoun, Christian K Pfaller, Roman H Khadka, Fang Jin, Jiaying Zheng, Matthew R Schuelke, Laura Evgin, et al. “SCIDOT-34. BRAIN INJURY SIGNALS SYSTEMIC IMMUNOSUPPRESSION THROUGH THYMIC INVOLUTION.” Neuro-Oncology 21, no. Supplement_6 (November 11, 2019): vi278–79. https://doi.org/10.1093/neuonc/noz175.1170.
Ayasoufi K, K Pfaller C, H Khadka R, Jin F, Zheng J, R Schuelke M, et al. SCIDOT-34. BRAIN INJURY SIGNALS SYSTEMIC IMMUNOSUPPRESSION THROUGH THYMIC INVOLUTION. Neuro-Oncology. 2019 Nov 11;21(Supplement_6):vi278–9.
Ayasoufi, Katayoun, et al. “SCIDOT-34. BRAIN INJURY SIGNALS SYSTEMIC IMMUNOSUPPRESSION THROUGH THYMIC INVOLUTION.” Neuro-Oncology, vol. 21, no. Supplement_6, Oxford University Press (OUP), Nov. 2019, pp. vi278–79. Crossref, doi:10.1093/neuonc/noz175.1170.
Ayasoufi K, K Pfaller C, H Khadka R, Jin F, Zheng J, R Schuelke M, Evgin L, J Hansen M, T Himes B, E Fain C, P Tritz Z, N Goddery E, T Yokanovich L, R Pease L, G Vile R, J Johnson A. SCIDOT-34. BRAIN INJURY SIGNALS SYSTEMIC IMMUNOSUPPRESSION THROUGH THYMIC INVOLUTION. Neuro-Oncology. Oxford University Press (OUP); 2019 Nov 11;21(Supplement_6):vi278–vi279.
Journal cover image

Published In

Neuro-Oncology

DOI

EISSN

1523-5866

ISSN

1522-8517

Publication Date

November 11, 2019

Volume

21

Issue

Supplement_6

Start / End Page

vi278 / vi279

Publisher

Oxford University Press (OUP)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1109 Neurosciences