Immuno-phenotyping of IDH-mutant grade 3 astrocytoma and IDH-wildtype glioblastoma reveals specific differences in cells of myeloid origin

Abstract

Gliomas are heavily infiltrated with immune cells of myeloid origin. Past studies have shown that high-grade gliomas have a higher proportion of alternatively activated and suppressive myeloid cells when compared to low-grade gliomas, which correlate with poor prognosis. However, the differences in immune cell phenotypes within high-grade gliomas (between grade 3 and grade 4 or GBM) are relatively less explored, and a correlation of phenotypic characteristics between immune cells in the blood and high-grade tumors has not been performed. Additionally, myeloid cells of granulocytic origin present in gliomas remain poorly characterized. Herein, we address these questions through phenotypic characterizations of monocytes and neutrophils present in blood and tumors of individuals with glioblastoma (GBM, IDH-wild type) or grade 3 IDH-mutant gliomas. We observe that neutrophils are highly heterogeneous among individuals with glioma, and are different from healthy controls. We also show that CD163 expressing M2 monocytes are present in greater proportions in GBM tissue when compared to grade 3 IDH-mutant glioma tissue, and a larger proportion of granulocytic myeloid-derived suppressor cells are present in grade 3 IDH-mutant gliomas when compared to GBM. Finally, we demonstrate that the expression levels of CD86 and CD63 showed a high correlation between blood and tumor and suggest that these may be used as possible markers for prognosis.

Ultralow-dose binary oncolytic/helper-dependent adenovirus promotes antitumor activity in preclinical and clinical studies

“…S7). To better understand how ULCA initially affected lymphocyte subpopulations, we phenotyped peripheral immune cells and detected an early and transient decrease in both NK cells and CD8 + T cells; CD206 + and CD15 + monocytes, associated with immunosuppressive monocytes ( 22 , 23 , 30 ), were unchanged in total numbers but increased as a proportion of total peripheral blood mononuclear cells (PBMCs) in all patients ( Fig. 5B and fig.…”

“…Nonetheless, ULCA treatment further increased the number of activated (CD56 + ) CD8 + T cells compared to controls (P = 0.0402). CD15 + monocytes, associated with immunosuppressive monocytes (22,23), were also reduced in ULCA-treated compared to control mice (P = 0.3485). Thus, in SUM-159 mice, ULCA enhanced infiltration of proinflammatory and cytotoxic T cells and reduced the presence of cells with a T reg (CD4 + , CD25 High , CTLA-4 High ) phenotype (P = 0.108).…”

scRNA‐seq and proteomics reveal the distinction of M2‐like macrophages between primary and recurrent malignant glioma and its critical role in the recurrence

“…Prior research has shown that IDH wild-type gliomas had significantly higher levels of MES-like malignant cells and M2 macrophage than IDH mutant gliomas. 42,61,65 While in IDH mutant gliomas, tumors with 1p/19q co-deletion exhibited significantly higher levels of NPC-like malignant cells and M2-related TAMs and lower levels of OPC-like malignant cells than tumors without 1p/19q co-deletion. 61 Consequently, intercellular interactions between MES-like malignant cells and M2-like TAMs may contribute more to the recurrence of IDH wild-type gliomas, which may further result in a more serious tumor-suppressive effect of immune cells due to the increase of CA9 in the IDH wild-type gliomas.…”

ITGAL infers adverse prognosis and correlates with immunity in acute myeloid leukemia

“…Among ten hub genes from the PPI analysis, CD86 and CD163 were biomarkers on the surface of M1- and M2-like macrophages respectively, and the high expression of CD86 and CD163 was related to the poor prognosis [ 31 ]. IL-10 secreted by M-MDSC plays a role in mediating tumor metastasis and suppressing immune response [ 32 ].…”