IMMU-24. THE IMPACT OF BRAIN TUMORS ON HEMATOPOIETIC STEM CELL-DERIVED T CELLS. (5th November 2018)

• Record Type: Journal Article
• Authors: Dean, Bayli DiVita; Fernandez, Brandon; Woodworth, Delaney; Wildes, Tyler; Mitchell, Duane; Flores, Catherine
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 6
• Page Start: vi126
• Page End: vi126
• 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/noy148.527
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: INTRODUCTION: The T cell repertoire of brain tumor bearing hosts has been previously described to be skewed to have increased regulatory phenotype relative to healthy hosts (Woroniecka et al 2018). We have found that hematopoietic stem cells (HSCs) isolated from tumor bearing mice are inefficient at engraftment and reconstitution of the hematopoietic compartment, giving rise to less live cells than HSCs derived from healthy controls. We found that CD4+ splenocytes and CD8+ bone marrow-derived cells and splenocytes that arise from HSCs of tumor bearing hosts are polarized towards a terminal memory phenotype relative to HSCs derived from healthy hosts. We believe that this dysregulation in T cell reconstitution is a major player in mounting immune responses against CNS malignancies. METHODS: Lineage negative HSCs were isolated from GFP transgenic healthy donors or DsRed transgenic tumor-bearing mice and adoptively transferred into C57BL/6 recipient cohort of lethally irradiated mice. HSCs are derived from DsRed or GFP transgenic mice to allow for tracking of HSC-derived populations. One month after transfer, mice are sacrificed and spleen, bone marrow, and blood are harvested and stained for flow cytometry. RESULTS & CONCLUSIONS: T cells derived from TB HSCs have a distinct phenotype compared to T cells from healthy HSCs, demonstrating intracranial brain tumors likely have an impact on HSC differentiation outcomes.