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The immune microenvironment is important for the development, progression, and prognosis of anaplastic glioma (AG). This complex milieu has not been fully elucidated, and a high-dimensional analysis is urgently required. Utilizing mass cytometry (CyTOF), we performed an analysis of immune cells from 5 patients with anaplastic astrocytoma, IDH-mutant (AAmut) and 10 patients with anaplastic oligodendroglioma, IDH-mutant and 1p/19q codeletion (AOD) and their paired peripheral blood mononuclear cells (PBMCs). Based on a panel of 33 biomarkers, we demonstrated the tumor-driven immune changes in the AG immune microenvironment. Our study confirmed that mononuclear phagocytes and T cells are the most abundant immunocytes in the AG immune microenvironment. Glioma-associated microglia/macrophages in both AAmut and AOD samples showed highly immunosuppressive characteristics. Compared to those in the PBMCs, the ratios of immune checkpoint-positive exhausted CD4+ T cells and CD8+ T cells were higher at the AG tumor sites. The AAmut immune milieu exhibits more immunosuppressive characteristics than that in AOD. [ABSTRACT FROM AUTHOR]

The Glioblastoma (GBM) immune microenvironment plays a critical role in tumor development, progression, and prognosis. A comprehensive understanding of the intricate milieu and its interactions remains unclear, and single-cell analysis is crucially needed. Leveraging mass cytometry (CyTOF), we analyzed immunocytes from 13 initial and three recurrent GBM samples and their matched peripheral blood mononuclear cells (pPBMCs). Using a panel of 30 markers, we provide a high-dimensional view of the complex GBM immune microenvironment. Hematoxylin and eosin staining and polychromatic immunofluorescence were used for verification of the key findings. In the initial and recurrent GBMs, glioma-associated microglia/macrophages (GAMs) constituted 59.05 and 27.87% of the immunocytes, respectively; programmed cell death-ligand 1 (PD-L1), T cell immunoglobulin domain and mucin domain-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), interleukin-10 (IL-10) and transforming growth factor-β (TGFβ) demonstrated different expression levels in the GAMs among the patients. GAMs could be subdivided into different subgroups with different phenotypes. Both the exhausted T cell and regulatory T (Treg) cell percentages were significantly higher in tumors than in pPBMCs. The natural killer (NK) cells that infiltrated into the tumor lesions expressed higher levels of CXC chemokine receptor 3 (CXCR3), as these cells expressed lower levels of interferon-γ (IFNγ). The immune microenvironment in the initial and recurrent GBMs displayed similar suppressive changes. Our study confirmed that GAMs, as the dominant infiltrating immunocytes, present great inter- and intra-tumoral heterogeneity and that GAMs, increased exhausted T cells, infiltrating Tregs, and nonfunctional NK cells contribute to local immune suppressive characteristics. Recurrent GBMs share similar immune signatures with the initial GBMs except the proportion of GAMs decreases. [ABSTRACT FROM AUTHOR]

The tumor immune microenvironment (TIME) plays a pivotal role in tumor development, progression, and prognosis. However, the characteristics of the TIME in diffuse astrocytoma (DA) are still unclear. Leveraging mass cytometry with a panel of 33 markers, we analyzed the infiltrating immune cells from 10 DA and 4 oligodendroglioma (OG) tissues and provided a single cell-resolution landscape of the intricate immune microenvironment. Our study profiled the composition of the TIME in DA and confirmed the presence of immune cells, such as glioma-associated microglia/macrophages (GAMs), CD8+ T cells, CD4+ T cells, regulatory T cells (Tregs), and natural killer cells. Increased percentages of PD-1+ CD8+ T cells, TIM-3+ CD4+ T cell subpopulations, Tregs and pro-tumor phenotype GAMs substantially contribute to the local immunosuppressive microenvironment in DA. DAs and OGs share similar compositions in terms of immune cells, while GAMs in DA exhibit more inhibitory characteristics than those in OG. [ABSTRACT FROM AUTHOR]