CLEC5A expressed on myeloid cells as a M2 biomarker relates to immunosuppression and decreased survival in patients with glioma

Abstract

Glioma is the most common tumor in the central nervous system that portends a poor prognosis. Key genes negatively related to survival may provide targets for therapy to improve the outcome of glioma. Here, we report a protein-coding gene CLEC5A, which is the top 1 gene by univariate Cox regression analysis of 524 primary GBM samples. Expression of CLEC5A is significantly correlated with decreased overall survival in patients with glioma via large-scale analysis. An analysis of 2589 patient samples showed that CLEC5A expression is higher in (1) glioblastoma than in lower-grade glioma and nontumor tissue, (2) in the mesenchymal subtype than in other subtypes, and (3) in IDH1-wild type glioblastoma than in IDH1-mutated glioblastoma. Notably, this tumor-associated biomarker is expressed preferentially on myeloid cells over glioma cells. And it shows a strong co-expression with M2 macrophage biomarker. Furthermore, CLEC5A-associated genes are enriched in immunosuppressive biological processes. The silico flow cytometry also showed CLEC5A expression related to less tumor purity and more tumor-promoting leukocytes infiltration. In conclusion, we proposed a new M2 biomarker expressed on myeloid cells that may decrease survival in patients with glioma through immunosuppressive mechanisms.

Identification of an Immune-Related Prognostic Gene CLEC5A Based on Immune Microenvironment and Risk Modeling of Ovarian Cancer

“…Co-culture assay showed that OC cells overexpressing CLEC5A could enhance the M2 polarization of M2 macrophages ( Figure 6D and Supplementary Figure 4C ). Moreover, overexpression of CLEC5A in M2 macrophages can also enhance its own M2 polarization ( Figure 6E ), as in a previous study ( Tong et al, 2020 ). The correlation analysis between CLEC5A and immune checkpoint gene suggested that CLEC5A was positively correlated with CD80, CD86, PD-L1, CTLA4, CD47, and PD-L2 ( Figure 6C ).…”

Lactobacillus plantarum‐derived extracellular vesicles induce anti‐inflammatory M2 macrophage polarization in vitro

“…However, it had no significant effect on the expression of other M1 macrophage markers, such as CD68 [ 21 ], TLR2 / TLR4 [ 46 ], which are highly expressed in THP1 cells (Supplementary Figure S5), and human leukocyte antigen-DR alpha ( HLA-DRα ) [ 18 , 21 ] ( Figure 4(a,b) ). In contrast, the majority of M2-related genes, including CD209 [ 47 ], C-type lectin domain family 5-member A ( CLEC5A ) [ 48 ], CD200 R [ 49 ], sphingosine kinase 1 ( SPHK1 ), class A scavenger receptor 1 ( SRA1 ) [ 50 ], IL1 receptor, type II ( IL1R2 ) [ 49 ], and CD163 [ 51 ], were significantly increased in LEV-treated, compared to vehicle-treated, cells ( Figure 4(a,c) ). The functional activity of LEVs in regulating the expression of macrophage-polarized genes was further verified using density-purified LEVs, which did not significantly increase the expression of M1-related genes (CD68, TLR2, HLA-DRα ), however did increase M2-related genes ( CLEC5A, SRA, CD163 ), and was specific when considering the effects driven by medium concentrates (Supplementary Figure S6).…”

Prognostic value and immune cell infiltration of hypoxic phenotype‐related gene signatures in glioblastoma microenvironment

“…For example, CLEC5A is a member of the C‐type lectin/C‐type lectin‐like domain (CTL/CTLD) superfamily and is reported to be an M2 biomarker, associated with immunosuppression. CLEC5A overexpression decreases survival time in glioma patients 29 . CHI3L1 encodes a glycoprotein member of the glycosyl hydrolase 18 family that is an immunomodulatory molecule, which may inhibit the PI3K/AKT pathway in GBM.…”