β2-Microglobulin Maintains Glioblastoma Stem Cells and Induces M2-like Polarization of Tumor-Associated Macrophages

Li, Daqi; Zhang, Qian; Li, Lu; Chen, Kexin; Yang, Jing; Dixit, Deobrat; Gimple, Ryan C.; Ci, Shusheng; Lu, Chenfei; Hu, Lang; Gao, Jiancheng; Shan, Danyang; Li, Yangqing; Zhang, Junxia; Shi, Zhumei; Gu, Danling; Yuan, Wei; Wu, Qiulian; Yang, Kailin; Zhao, Linjie; Qiu, Zhixin; Lv, Deguan; Gao, Wei; Yang, Hui; Lin, Fan; Wang, Qianghu; Man, Jianghong; Li, Chao‐Jun; Tao, Weiwei; Agnihotri, Sameer; Qian, Xu; Shi, Yu; You, Yongping; Zhang, Nu; Rich, Jeremy; Wang, Xiuxing

doi:10.1158/0008-5472.can-22-0507

Cited by 48 publications

(39 citation statements)

References 53 publications

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“…We found that porcine M2_IL4 + IL10 highly expressed PPARG , NTRK1 , ADIPOQ , FLT1 , HMOX1 , and M2_M-CSF highly expressed IL6 , CD4 , IGF1 , IL10 , PTGS2 , FOS , PPARG [ 50 , 51 , 52 ]. PPARG has an anti-inflammatory effect, and its ligand is responsible for clearing the expression of genes of apoptotic cells and macrophage-mediated inflammatory responses [ 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Establishment of Pig Macrophage Polarization Signatures

Yuan

Zhang

et al. 2023

CIMB

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Macrophages are the foremost controllers of innate and acquired immunity, playing important roles in tissue homeostasis, vasculogenesis, and congenital metabolism. In vitro macrophages are crucial models for understanding the regulatory mechanism of immune responses and the diagnosis or treatment of a variety of diseases. Pigs are the most important agricultural animals and valuable animal models for preclinical studies, but there is no unified method for porcine macrophage isolation and differentiation at present; no systematic study has compared porcine macrophages obtained by different methods. In the current study, we obtained two M1 macrophages (M1_IFNγ + LPS, and M1_GM-CSF) and two M2 macrophages (M2_IL4 + IL10, and M2_M-CSF), and compared the transcriptomic profiles between and within macrophage phenotypes. We observed the transcriptional differences either between or within phenotypes. Porcine M1 and M2 macrophages have consistent gene signatures with human and mouse macrophage phenotypes, respectively. Moreover, we performed GSEA analysis to attribute the prognostic value of our macrophage signatures in discriminating various pathogen infections. Our study provided a framework to guide the interrogation of macrophage phenotypes in the context of health and disease. The approach described here could be used to propose new biomarkers for diagnosis in diverse clinical settings including porcine reproductive and respiratory syndrome virus (PRRSV), African swine fever virus (ASFV), Toxoplasma gondii (T. gondii), porcine circovirus type 2 (PCV2), Haemophilus parasuis serovar 4 (HPS4), Mycoplasma hyopneumoniae (Mhp), Streptococcus suis serotype 2 (SS2), and LPS from Salmonella enterica serotype minnesota Re 595.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic Establishment of Pig Macrophage Polarization Signatures

Yuan

Zhang

et al. 2023

CIMB

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“…Accumulating data suggest that B2M is involved in a wide range of physiological and pathological functions, such as cell proliferation and apoptosis, and is also regarded as an important prognostic factor and predictor of survival associated with multiple cancers. B2M activates the PI3K/AKT/mTOR signaling pathway by promoting secretion of transforming growth factor-β1 (TGFβ1) ( 26 ). The CRISPR-Cas9 system was used to develop CAR T cells with three types of gene editing, including that in the B2M.…”

Section: Discussionmentioning

confidence: 99%

Novel potential biomarkers for severe alcoholic liver disease

Huang

Wang

et al. 2022

Front. Immunol.

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BackgroundAlcoholic liver disease (ALD) is a leading cause of advanced liver disease; however, minor clinical symptoms in the early stage frequently result in delayed diagnosis and therapy. Invasive liver biopsy, the gold standard for diagnosing ALD, is unsuitable for repetitive analysis. This study aims to identify potential serum biomarkers that could contribute to non-invasive disease screening and monitoring.MethodsLabel-free LC-MS/MS quantitative proteomics analysis was performed to identify differentially expressed proteins in the discovery cohort, followed by bioinformatics analysis based on the KEGG, GO, and String databases. Prioritized proteins were validated subsequently by quantitative assays. The area under the receiver operating characteristic curve (AUROC) was used to assess the diagnosis performance of potential biomarkers.ResultsA total of 161 differentially expressed proteins were identified in the discovery cohort, of which 123 were up-regulated and 38 were down-regulated. B2M, IGFALS, and IGFBP3 were evaluated, and all demonstrated excellent diagnosis performance with AUROCs of over 0.9 when distinguishing patients with severe ALD from healthy controls. The AUROC values of B2M, IGFBP3, and IGFALS were 0.7131, 0.8877, and 0.9896 for differentiating severe ALD from non-severe ALD to indicate disease severity. B2M could distinguish patients with non-severe ALD and HC participants with an AUROC value of 0.8985. The efficiency of multiple combinations of these biomarkers was superior to that of the existing liver fibrosis evaluation indices used to monitor disease progression, with AUROC values of over 0.9. IGFALS showed a positive correlation with ALT/AST (r=0.4648, P=0.0009) and may be developed as a therapeutic target.ConclusionThis proteomic study identified three novel candidate proteins as promising circulating biomarkers for clinical diagnosis and disease progression and also provided the proteomic atlas for ALD pathophysiological mechanisms.

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“…Conversely, GAMs have been shown to play a role in promoting GSCs ( 119 – 122 ). Research by Wang et al.…”

Section: Interaction Between Gams and Gbm Cellsmentioning

confidence: 99%

“…Conversely, GAMs have been shown to play a role in promoting GSCs (119)(120)(121)(122). Research by Wang et al demonstrated that IL-6, which is secreted by microglia, can function as a growth factor for GSCs and enhance their biological function (122).…”

Section: Interactions Between Gams and Gscsmentioning

confidence: 99%

Glioma-associated microglia/macrophages (GAMs) in glioblastoma: Immune function in the tumor microenvironment and implications for immunotherapy

Lin

Wang

2023

Front. Immunol.

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Glioma is a mixed solid tumor composed of neoplastic and non-neoplastic components. Glioma-associated macrophages and microglia (GAMs) are crucial elements of the glioma tumor microenvironment (TME), regulating tumor growth, invasion, and recurrence. GAMs are also profoundly influenced by glioma cells. Recent studies have revealed the intricate relationship between TME and GAMs. In this updated review, we provide an overview of the interaction between glioma TME and GAMs based on previous studies. We also summarize a series of immunotherapies targeting GAMs, including clinical trials and preclinical studies. Specifically, we discuss the origin of microglia in the central nervous system and the recruitment of GAMs in the glioma background. We also cover the mechanisms through which GAMs regulate various processes associated with glioma development, such as invasiveness, angiogenesis, immunosuppression, recurrence, etc. Overall, GAMs play a significant role in the tumor biology of glioma, and a better understanding of the interaction between GAMs and glioma could catalyze the development of new and effective immunotherapies for this deadly malignancy.

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β2-Microglobulin Maintains Glioblastoma Stem Cells and Induces M2-like Polarization of Tumor-Associated Macrophages

Cited by 48 publications

References 53 publications

Transcriptomic Establishment of Pig Macrophage Polarization Signatures

Transcriptomic Establishment of Pig Macrophage Polarization Signatures

Novel potential biomarkers for severe alcoholic liver disease

Glioma-associated microglia/macrophages (GAMs) in glioblastoma: Immune function in the tumor microenvironment and implications for immunotherapy

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