Systemic Lymphoid Architecture Response Assessment (SYLARAS): An approach to multi-organ, discovery-based immunophenotyping implicates a role for CD45R/B220+ CD8T cells in glioblastoma immunology [article]

Gregory J. Baker, Sucheendra K. Palaniappan, Jodene K. Moore, Stephanie H. Davis, Sandro Santagata, Peter K. Sorger
2019 bioRxiv   pre-print
Investigational and computational methods for the systematic exploration of global immune response are needed to gain a more integrated comprehension of disease and to explore the mechanisms of immunotherapy. Here were describe a modular and extensible framework for the acquisition, analysis, and visual display of systems-level immunophenotyping data called SYLARAS (Systemic Lymphoid Architecture Response Assessment, www.sylaras.org). Leveraging our technology against a syngeneic mouse model of
more » ... neic mouse model of glioblastoma (GBM) brain cancer, we reveal tumor-induced perturbation in the frequency and cell-to-cell co-variation of peripheral immune cell subsets hitherto undescribed in the disease. The most novel and significant of our findings relates to a population of CD8+ T cells characterized by their expression of the CD45R/B220 isoform of the leukocyte common antigen, CD45 (aka B220+ CD8T cells). In follow-on studies, we demonstrate that mouse B220+ CD8T cells are a transcriptionally and morphologically-distinct subset of GBM-infiltrating lymphocytes whose human analog is identified in normal human blood and a subset of primary and recurrent GBM clinical biopsies. The ability of cells of this immunophenotype to attenuate immune response to autologous antigens, as demonstrated by the work of others, suggests that B220+ CD8T cells may play an immunoregulatory role in GBM. By providing ample content for inductive scientific inference in the era of immunotherapy, SYLARAS has the potential to uncover complex cell and molecular mechanisms governing immunologic response.
doi:10.1101/555854 fatcat:olufyfbzzjecza5x2nbq3pvsjm