Increase in Both CD14-Positive and CD15-Positive Myeloid-Derived Suppressor Cell Subpopulations in the Blood of Patients With Glioma But Predominance of CD15-Positive Myeloid-Derived Suppressor Cells in Glioma Tissue

Abstract

Myeloid-derived suppressor cells (MDSCs), defined as CD33-positive major histocompatibility complex class II-negative cells, are increased in a variety of human tumors and are associated with immunosuppression. Myeloid-derived suppressor cells can be further subdivided into CD14-positive monocytic MDSC and CD15-positive granulocytic MDSC (polymorphonuclear MDSC) subpopulations. Here we analyzed MDSC subsets in the blood and tumor tissue of patients with glioma, including the most malignant variant, glioblastoma multiforme (GBM). CD33-positive major histocompatibility complex class II-negative MDSCs in blood from 21 patients with glioma and 12 healthy individuals were phenotyped and quantified by flow cytometry. Myeloid populations of the monocytic MDSC and polymorphonuclear MDSC phenotypes were both significantly increased in the blood of patients with GBM versus healthy controls. The myeloid activation markers CD80 and PD-L1 could not be detected on either of these MDSC subsets; CD124, CD86, and CD40 were detected at similar levels on MDSCs in patients with glioma and healthy donors. By contrast, in tumor cell suspensions, the MDSC population consisted almost exclusively of CD15-positive cells. Immunohistochemistry confirmed infiltration of CD15-positive major histocompatibility complex class II-negative cells in glioma tissue samples. These data support a role for cells with an MDSC phenotype in the blood and tumor microenvironment of patients with GBM.

Glioblastoma-infiltrated innate immune cells resemble M0 macrophage phenotype

“…Our finding of elevated numbers of monocytic MDSCs in glioblastoma patients is consistent with a previous report that these cells represent a major subpopulation of MDSCs in the blood of glioblastoma patients (20). Additionally, it has been shown that patients with advanced cancer have high levels of blood neutrophilia (61), which we observed in glioblastoma patients as well.…”

“…We did not find a significant difference in the number of monocytes between glioblastoma patients who were given steroids prior to resection at the time of blood draw and those not given steroids (Supplemental Figure 1B). Researchers have defined immune-suppressive neutrophilic and monocytic MDSCs based on their surface expression of CD33 + CD11b + CD14 − CD15 + and CD33 + CD11b + CD14 + CD15 − , respectively (20, 21). In the blood of glioblastoma patients, we identified three myeloid cell populations: the predominant monocytic subset of MDSCs (CD33 + CD11b + CD14 high CD15 − ), a minor population of neutrophilic MDSCs expressing CD33 + CD11b + CD14 low CD15 + , and CD11b + CD14 low monocytes (Supplemental Figure 1, C and D).…”

Myeloid-derived suppressor cells in gliomas

“…1). Moreover, this heterogeneous population is composed of cells defined as CD14 + monocytic MDSC (CD11b + CD33 + C14 + ) and CD15 + granulocytic MDSC (CD11b + CD33 + CD15 + CD14 – ) [4]. Human MDSCs commonly express Siglec-3/CD33 and lack lineage markers and HLA-DR, but heterogeneous expression of CD14 and CD15 suggests the presence of multiple subsets.…”

Aneustat (OMN54) has aerobic glycolysis‐inhibitory activity and also immunomodulatory activity as indicated by a first‐generation PDX prostate cancer model

“…In contrast, as shown in Figure 5 b , Aneustat very markedly reduced the numbers of FOXP3 + Treg cells (by >90%), thereby markedly increasing the ratio of intratumoral patient anticancer T cells to Treg cells in the Aneustat‐treated tissues. NK cells and MDSCs were identified by staining with NCR1 and CD33, respectively 35, 36, 37. As shown in Figure 6, the Aneustat‐treated tissues showed higher NCR1 + NK cell numbers compared to controls, whereas the MDSCs in the Aneustat‐treated tissues were lower in number than in the controls.…”