Abstract LB-356: Deep immune profiling of de novo and recurrent glioblastoma

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Abstract To understand potential immune system alterations in glioblastoma patients and provide a foundation for immunotherapy, we profiled intra tumoral leucocytes from newly diagnosed de novo patients as well as patients with recurrent tumor using high dimensional CyTOF. All recurrent patients underwent standard-of-care therapy, including surgical resection, concurrent temozolomide and radiotherapy, and adjuvant temozolomide. We used two immune profiling panels: a broad profiling panel that includes 45 phenotypic markers that together permit the identification and enumeration of the main innate and adaptive immune cell subsets in humans, and a deep profiling panel that includes 45 features focused on T cell phenotype and biology. We report in both de novo and recurrent tumors a predominant infiltration by CD11b+CD14+ monocytes (43.6±13%. of CD45+ cells). These monocytes displayed an immunomodulatory M2 profile (CD163+HLA-DR-/+CD80-CD86-/+). The adaptive compartment was sparse and dominated by alpha beta T cells, although some mucosal associated invariant T cells and gamma delta T cells were also present. T cells were both conventional T cells and regulatory T cells. The latter tended to be more abundant in the de novo as compared to recurrent tumors (22.8±17.9% of CD4+ T cells in de novo vs 12.9±12.5% in recurrent tumors, P=0.09). Conventional T cells were mostly CD27-CD45RA- effectors, with high expression of PD1 (69.9±17.6% of CD8+ T cells). Using high dimensional approaches, we confirmed that this high expression of PD1 reflects T cell exhaustion, as defined by co-expression of other inhibitory receptors such as Tim3, CTLA-4 and LAG-3. Exhausted T cells typically co-expressed PD1 and CD39 in the de novo tumors, and this pattern was less often observed in recurrent tumors (63.4±22.84% of CD8+ T cells in de novo vs 46.3±14.5% in recurrent tumors, P=0.03). Together, our results highlight the potential issue of a substandard T cell compartment at the time of GBM diagnosis. We are now investigating the mechanisms underlying these observations, as well as their impact on T cell immunity of the patients, as well as current immunotherapy strategies. Our studies should provide a foundation for improving therapy in glioblastoma patients. Citation Format: Cécile Alanio, Zev A. Binder, Donald M. O'Rourke, E. John Wherry. Deep immune profiling of de novo and recurrent glioblastoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-356.