CD163, a novel therapeutic target, regulates the proliferation and stemness of glioma cells via casein kinase 2

Chen, Taoliang; Chen, Jiansheng; Zhu, Ying; Li, Yan; Wang, Yun; Chen, Huajian; Wang, Jihui; Li, Xiao; Liu, Yang; Li, Baisheng; Sun, Xinlin; Ke, Yiquan

doi:10.1038/s41388-018-0515-6

Cited by 51 publications

(43 citation statements)

References 57 publications

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“…Cancer stem cells (CSCs) are defined as a small subpopulation of cells in the tumors that possess the ability to initiate neoplasms and sustain tumor self-renewal. It has been suggested that CSCs rely on a TME niche, demonstrated using knockdown experiments that CD163 promoted cell proliferation and stemness [ 11 ], thereby contributing to tumorigenesis. This could be, at least partially explained, because CD163 contributes to regulating the transcription of cyclin D1, CD133, ALDH1A1, NANOG, and OCT4 [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…Antibodies against CD68, a pan-macrophage marker, allows to identify all macrophages regardless of their phenotype, while the CD163 marker is a transmembrane scavenger receptor for haptoglobin–hemoglobin, highly expressed by M2 macrophages, and as such it has been widely recognized and used as marker for M2 macrophages [ 7 ]. CD163 has an essential role in eliminating hemoglobin–haptoglobin complexes and inducing the innate immune response [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…Macrophages are the most important ancillary cells regulating CSC activities [ 1 ]. However, the functional role of TAMs in OSCC is poorly understood, and the possible relationship between TAM infiltration and CSC phenotypes has not been investigated yet in oral carcinogenesis [ 11 ]. Among the numerous CSCs markers, NANOG and SOX2 have recently been identified as predictors of oral cancer risk in patients with oral precancerous lesions [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Macrophages in Oral Carcinomas: Relationship with Cancer Stem Cell Markers and PD-L1 Expression

Suárez-Sánchez

Lequerica-Fernández

Suárez-Canto

et al. 2020

Cancers

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Tumor-associated macrophages (TAMs) can be polarized into antitumoral M1 and protumoral and immunosuppressive M2 macrophages. This study investigated the clinical relevance of TAM infiltration in oral squamous cell carcinoma (OSCC), evaluating CD68 (M1 and M2 macrophage marker) and CD163 expression (M2 macrophage marker) in the tumor nests and surrounding stroma. Immunohistochemical analysis of both stromal/tumoral CD68+ and CD163+ TAMs was performed in paraffin-embedded tissue specimens from 125 OSCC patients, and correlated with clinical data. Potential relationships with the expression of cancer stem cell (CSC) markers and PD-L1 in the tumors were also assessed. Stromal CD163+ infiltration was significantly associated with the tumor location in the tongue, and stromal and tumoral CD68+ and CD163+-infiltrating TAMs were more abundant in nonsmokers and non-alcohol-drinkers. Strikingly, this study uncovers an inverse relationship between CD68+ and CD163+ TAMs and CSC marker expression (NANOG and SOX2) in OSCC. High infiltration of CD163+ TAMs in both tumor and stroma was strongly and significantly correlated with the absence of NANOG expression. Moreover, infiltration of both CD68+ and CD163+ TAMs was also significantly associated with high tumor expression of PD-L1. Our results suggest that there is a link between TAM infiltration and immune escape in OSCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Macrophages in Oral Carcinomas: Relationship with Cancer Stem Cell Markers and PD-L1 Expression

Suárez-Sánchez

Lequerica-Fernández

Suárez-Canto

et al. 2020

Cancers

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“…In CSF from glioblastoma patients, only 2 mRNAs are significantly upregulated compared to CSF from hydrocephalus patients. CD163, one of the upregulated genes in glioblastoma, has been linked with glioblastoma pathogenesis 39 . In saliva from diabetes patients and saliva from healthy volunteers, no differentially expressed genes could be identified.…”

Section: Assessment Of the Tissues Of Origin And Deconvolution Of Panmentioning

confidence: 99%

Charting extracellular transcriptomes in The Human Biofluid RNA Atlas

Hulstaert

Morlion

Cobos

et al. 2019

Preprint

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Extracellular RNAs present in biofluids have emerged as potential biomarkers for disease.Where most studies focus on plasma or serum, other biofluids may contain more informative RNA molecules, depending on the type of disease. Here, we present an unprecedented atlas of messenger, circular and small RNA transcriptomes of a comprehensive collection of 20 different human biofluids. By means of synthetic spike-in controls, we compared RNA content across biofluids, revealing a more than 10 000-fold difference in RNA concentration. The circular RNA fraction is increased in nearly all biofluids compared to tissues. Each biofluid transcriptome is enriched for RNA molecules derived from specific tissues and cell types. In addition, a subset of biofluids, including stool, sweat, saliva and sputum, contains high levels of bacterial RNAs. Our atlas enables a more informed selection of the most relevant biofluid to monitor particular diseases. To verify the biomarker potential in these biofluids, four validation cohorts representing a broad spectrum of diseases were profiled, revealing numerous differential RNAs between case and control subjects. Taken together, our results reveal novel insights in the RNA content of human biofluids and may serve as a valuable resource for future biomarker studies.

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“…In tissues, CD163 is mainly resident in tissue macrophages [26], and CD163 is considered the most speci c marker of TAMS [27,28]. Recent studies have reported that CD163 can promote the occurrence of glioma through CK2 and may be a potential new target for glioma treatment [29,30], and closely related to EMT in other cancers [31,32]. But the association and function of CD163 with immune checkpoint genes and EMT in GBM is yet to be examined.…”

Section: Introductionmentioning

confidence: 99%

The High Expression of CD276/HAVCR2 and CD163 is an Adverse Immune Subtype of Glioblastoma and is Closely Related to Epithelial-Mesenchymal Transition

Hou

Zhou

Fan

et al. 2020

Preprint

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Background Glioblastoma (GBM) is one of the most malignant tumors that can afflict the central nervous system. Previous studies have observed that there are individual differences in the treatment response of immune checkpoint inhibitors in glioblastoma. This study’s aim is to ascertain the factors that may affect the efficacy of immunosuppressant therapy. Methods The clinical data of this study were obtained from a public database. Then, the data was analyzed and processed by R software and corresponding R package. To verify the results of the analysis, information was gathered from 89 GBM patients in our hospital and thereafter the corresponding paraffin sections were stained and quantitatively analyzed by immunohistochemistry. Results From the analysis, it was observed that both CD276 and HAVCR2 were significantly overexpressed in GBM and could be associated with patient prognosis. The analysis of single cell RNA sequencing data and GBM data analysis found an immune subtype with poor prognosis. Further analysis found that the high expression of CD276, HAVCR2 and CD163 was closely related to epithelial-mesenchymal transition (EMT) and could affect the patient prognosis of PD-L1 high expression. GSVA enrichment analysis showed that CD276, HAVCR2 and CD163 might induce EMT by JAK-STAT3 signaling pathway, and RUNX1 and IKZF1 might be transcription factors that regulate CD276/HAVCR2 high expression. Conclusions We found an immune subtype with poor prognosis of GBM, the high expression of CD276, HAVCR2 and CD163 with EMT are closely related and may be one of the factors affecting the efficacy of Anti-PD-L1.

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CD163, a novel therapeutic target, regulates the proliferation and stemness of glioma cells via casein kinase 2

Cited by 51 publications

References 57 publications

Macrophages in Oral Carcinomas: Relationship with Cancer Stem Cell Markers and PD-L1 Expression

Macrophages in Oral Carcinomas: Relationship with Cancer Stem Cell Markers and PD-L1 Expression

Charting extracellular transcriptomes in The Human Biofluid RNA Atlas

The High Expression of CD276/HAVCR2 and CD163 is an Adverse Immune Subtype of Glioblastoma and is Closely Related to Epithelial-Mesenchymal Transition

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