Characterization of transcriptome profile and clinical features of a novel immunotherapy target CD204 in diffuse glioma

Abstract

CD204 is a specific marker of tumor‐associated macrophages (TAMs) in glioma. However, the expression levels of CD204 and its involvement in glioma are not fully understood. In this large‐scale study, we assessed the expression and function of CD204 in whole‐grade glioma molecularly and clinically. In total, 1323 glioma samples, including 301 microarray data and 325 RNA‐seq data from the Chinese Glioma Genome Atlas (CGGA) dataset and 697 RNA‐seq data from The Cancer Genome Atlas (TCGA) dataset, were utilized. The statistical analysis and graphical work were mainly performed using the R software. Univariate and multivariate Cox analysis demonstrated that CD204 was an independent prognosticator in glioma patients. CD204 expression was positively correlated with the grade of malignancy. CD204 was consistently upregulated in wild‐type isocitrate dehydrogenase glioma and highly expressed in mesenchymal glioblastoma. Gene ontology of CD204‐related genes showed that CD204 was most enriched in inflammatory response and immune response. It was associated with the stromal and immune populations, especially the monocytic lineage, fibroblasts, and T cells. Circos plots revealed that CD204 was closely associated with many immune checkpoint regulators, especially TIM‐3. CD204 expression is consistent with the malignant phenotype of glioma and independently predicts poor outcomes in glioma patients. Additionally, CD204 + TAMs, collaborating with other checkpoint members, may contribute to the dysfunction of T cells. These findings suggest that CD204 may be a promising target for glioma immunotherapy.

A novel gene signature based on five immune checkpoint genes predicts the survival of glioma

“…The signature was highly related but independent to classic molecular characteristics such as IDH status, MGMT promoter methylation, and TCGA subtype, which is consistent with some previous work by us and others [ 16 - 18 ]. The univariate and multivariate Cox result confirmed the signature to function as an independent prognostic factor with higher predictive accuracy than other clinicopathologic characteristics.…”

A machine learning analysis of a “normal-like” IDH-WT diffuse glioma transcriptomic subgroup associated with prolonged survival reveals novel immune and neurotransmitter-related actionable targets

“…The class A macrophage scavenger receptor (MSR1 or CD204 gene) is expressed by tumor-associated M2 macrophages that induce tumor progression and angiogenesis by suppressing immunity in the tumor microenvironment [56]. The discovery of CD204 underexpression in normal-like IDH-WT is in line with findings from other studies, supporting the notion that CD204 expression is correlated with worse survival in cancer, including IDH-WT gliomas [57][58][59].…”

Inflammation and lymphocyte infiltration are associated with shorter survival in patients with high-grade glioma

“…6 The prognostic relevance of TAMs in highgrade glioma was shown to be positive, negative or absent in different studies, 7 but, generally, M2-like markers were positively associated with grade of malignancy and with poor survival in glioma. [7][8][9] Other cell types, such as myeloid-derived suppressor cells (MDSCs), have been described predominantly in the invasive margins of glioma samples, and MDSCs presence was shown to correlate with an unfavorable outcome. 3 Recent studies in glioma patients [10][11][12] have characterized gene signatures related to single immune markers and reported a correlation between myeloid marker expression and poor prognosis in GBM; however myeloid cell marker expression did not correlate with grade in glioma.…”

“… 6 The prognostic relevance of TAMs in high-grade glioma was shown to be positive, negative or absent in different studies, 7 but, generally, M2-like markers were positively associated with grade of malignancy and with poor survival in glioma. 7 – 9 …”