IMMU-20. SINGLE CELL CYTOMICS OF PERIPHERAL BLOOD MONONUCLEAR CELLS REVEALS NEW AVENUES FOR GLIOMA IMMUNOTHERAPY

Abstract

Glioblastoma is the most common primary brain tumor with a dismal prognosis and a lack of effective treatment options after relapse. Despite striking successes that were achieved in the last decade in other types of cancer, evidence of sustainable responses to T cell directed immunotherapy in glioblastoma remains limited. This might be explained by an emerging hypothesis that glioblastomas are cold tumours with poor lymphocyte infiltration. Therefore, some recent efforts have been focused on increasing cytotoxic lymphocyte infiltration. Here we present our workflow for subpopulation frequency, marker expression, and correlation network (INFERENCE) analysis, in this study applied to screen for possible new targets to enhance antiglioblastoma immune responses. Using high-dimensional, single-cell mass cytometry (CyTOF) we profiled peripheral blood mononuclear cells derived from 160 patients with glioblastoma, lower grade glioma, or metastasis, meningioma and epilepsy as controls. Based on a CyTOF panel composed mainly of lymphocyte markers and check-point inhibition markers we could effectively dissect blood leukocytes into 100 phenotypically separate subsets of CD4 T cells (35 subsets), CD8 T cells (17 subsets), monocytes (12 subsets), NK cells (14 subsets), and B cells (15 subsets), and map their frequencies, phenotypes and correlation statistics. We thereby created an in depth human atlas of peripheral blood mononuclear cells in patients with different types of intracranial tumors. Interestingly, a subset of B cells characterized by high expression of the Interleukin-2 receptor alpha chain (CD25, a typical marker of regulatory T cells) was significantly increased in glioblastoma patients. This immune suppressive B cell subset has previously been associated with enhancing the suppressive effect of regulatory T cells. Further research is warranted to investigate the role of this aberrant B cell subset in the context of glioblastoma and its potential as target for immunotherapy.