Galectin-9: A Suppressor of Atherosclerosis?

Yu, Jian; Zhu, Ruirui; Yu, Kunwu; Wang, Yue; Ding, Yan; Zhong, Yucheng; Zeng, Qiutang

doi:10.3389/fimmu.2020.604265

Cited by 14 publications

(11 citation statements)

References 44 publications

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“…It has been proven that Galectin-9 expression is closely correlated with the growth and metastasis of many solid cancers by inducing apoptosis of specific T cell subpopulations to mediate tumor immune escape ( 28 , 47 ). In contrast, our analyses revealed that high stromal Galectin-9 or PD-L1 expression in chordoma was associated with less aggressive tumor features and accurately reflected better prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, researchers identified several other immune checkpoint molecules that are aberrantly expressed in cancers and can hamper antitumor immunity to promote tumor progression via various mechanisms ( 25 – 28 ), such as human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2), B7H3, indoleamine 2,3-dioxygenase (IDO-1) and galectin-9. These findings suggest that other immune checkpoint molecules represent additional immunosuppressive mechanisms within the tumor microenvironment, which may have implications for immunotherapy combinations or the development of novel immunotherapy strategies in the future.…”

Section: Introductionmentioning

confidence: 99%

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Coexpression of HHLA2 and PD-L1 on Tumor Cells Independently Predicts the Survival of Spinal Chordoma Patients

Xia

Huang

Chen³

et al. 2022

Front. Immunol.

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BackgroundImmunotherapy only achieves efficacy in some cancer patients, and less is known about other immune checkpoint molecules in chordoma. Here, we aimed to determine the expression of PD-L1, HHLA2, B7H3, IDO-1 and Galectin-9 in spinal chordoma and evaluated their association with tumor infiltrating lymphocytes (TILs), clinicopathological characteristics and survival of patients.MethodsUsing multiplexed quantitative immunofluorescence (QIF), we simultaneously measured the levels of five different immune checkpoint molecules and major TIL subsets in 92 human spinal chordoma samples.ResultsTumor HHLA2 and PD-L1 were positive in 80.0% and 86.0% of cases, respectively. However, B7H3, IDO-1 and Galectin-9 positivity on tumor cells were only seen in 21.0% of cases, despite all showing predominantly stromal expression. Coexpression of these QIF markers in the tumor compartment was scarcely detected except for PD-L1 and HHLA2, which was observed in 69.6% of cases. While tumoral HHLA2 and stromal B7H3 expressions were associated with an aggressive tumor phenotype, suppressive immune response (specifically including elevated PD-1+ TILs level and decreased CD8+ TIL density) and poor prognosis, stromal levels of PD-L1 and Galectin-9 predicted the opposite outcomes. Importantly, HHLA2 and PD-L1 coexpression on tumor cells independently predicted both worse local recurrence-free survival and overall survival.ConclusionThese data provide a better understanding of the immunosuppressive mechanism in chordoma and may be useful for the development of combination or novel immunotherapy approaches aiming to improve therapeutic efficacy and survival.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Coexpression of HHLA2 and PD-L1 on Tumor Cells Independently Predicts the Survival of Spinal Chordoma Patients

Xia

Huang

Chen³

et al. 2022

Front. Immunol.

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“…Galectin-9 (coded by LGALS9 gene) is a crucial regulator of T-cell immunity by inducing apoptosis in specific T-cell subpopulations associated with autoimmunity and inflammatory disease. 37 About half of the CD4+ T cell clusters showed L-selectin (SELL) interaction with PSGL-1 (SELPLG) in both CVD+ and DM+ subjects ( Figure 7A, B ). Multiple studies have provided evidence supporting a key role for SELP and SELPLG in atherosclerotic lesion formation, thrombosis, and arterial wall changes.…”

Section: Resultsmentioning

confidence: 99%

Sex differences in coronary artery disease and diabetes revealed by scRNA-Seq and CITE-Seq of human CD4+ T cells

Saigusa

Vallejo

Gulati

et al. 2022

Preprint

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BackgroundDespite the decades-old knowledge that diabetes mellitus (DM) is a major risk factor for cardiovascular disease (CVD), the reasons for this association are only partially understood. Among the immune cells involved in CVD development, accumulating evidence supports the critical role of T cells as drivers and modifiers of this condition. CD4+ T cells are commonly found in atherosclerotic plaques. The activity and distribution of CD4+ T cell subsets differs between the sexes.MethodsPeripheral blood mononuclear cells (PBMCs) of 61 men and women who underwent cardiac catheterization were interrogated by single cell RNA sequencing (scRNA-Seq, ∼200,000 cells) combined with 49 protein markers (CITE-Seq). Coronary artery disease (CAD) was quantified using Gensini scores, with scores above 30 considered CAD+ and below 6 considered CAD-. Four pairs of groups were matched for clinical and demographic parameters. To test how DM changed cell proportions and gene expression, we compared matched groups of diabetic and non-diabetic subjects. We analyzed 41,782 single CD4+ T cell transcriptomes for sex differences in 61 mostly statin-treated coronary artery disease patients with and without DM.ResultsWe identified 16 clusters in CD4 T cells. The proportion of cells in CD4 cluster 8 (CD4T8, CCR2+ Em) was significantly decreased in CAD+, especially among DM+ participants. The proportions of cells in CD4T2, CD4T11, CD4T16 were increased and CD4T13 was decreased in CAD+ among DM+Statin+ participants. CD4T12 was increased in DM+ participants. In female participants, CD4T8, 12, and 13 were decreased compared to in male participants. In CD4 T cells, 31 genes showed significant and coordinated upregulation in both CAD and DM. The DM gene signature was partially additive to the CAD gene signature.ConclusionsWe conclude that CAD and DM are clearly reflected in PBMC transcriptomes and that significant differences exist between women and men and between subjects treated with statins or not.

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“…LGALS9 (galectin-9) was firstly characterized as a chemoattractant for eosinophils. Recent lines of evidence have implicated that LGALS9 is a multifaceted immune regulator in multiple cell types [49]. LGALS9, as a ligand of T cell immunoglobulin mucin 3 (Tim-3), can regulate the function of a variety of AS-associated immune cells, including effector T cells and macrophages, especially regulatory T cells [49].…”

Section: Discussionmentioning

confidence: 99%

Exploration of the Crucial Genes and Molecular Mechanisms Mediating Atherosclerosis and Abnormal Endothelial Shear Stress

et al. 2022

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Background. Abnormal endothelial shear stress (ESS) is a significant risk factor for atherosclerosis (AS); however, the genes and pathways between ESS and AS are poorly understood. Here, we screened hub genes and potential regulatory targets linked to the progression of AS induced by abnormal ESS. Methods. The microarray data of ESS and AS were downloaded from the Gene Expression Omnibus (GEO) database. The coexpression modules related to shear stress and AS were identified with weighted gene coexpression network analysis (WGCNA). Coexpression genes in modules obtained from GSE28829 and GSE160611 were considered as SET1. The results were validated in validation set by differential gene analysis. The limma package in R was used to identify differentially expressed genes (DEGs). The common DEGs of GSE100927 and GSE103672 were regarded as SET2. Next, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted. Protein-protein interaction (PPI) enrichment analysis was assembled, and hub genes were identified using MCODE and ClueGO in Cytoscape. ROC curve analyses were conducted to assess the ability of common hub genes to distinguish samples of atherosclerotic plaque from normal arterial. The expression of common hub gene was verified in ox-LDL-induced foam cells and GSE41571. Results. We identified three gene modules (the blue, tan, and cyan modules) related to AS and three shear stress-related modules (the brown, red, and pink modules). A total of 129 genes in SET1 and 476 genes in SET2 were identified. CCRL2, LGALS9, and PLCB2 were identified as common hub genes and validated in the GSE100927, GSE28829, and GSE41571. ROC analysis indicates the expression of CCRL2, LGALS9, and PLCB2 could effectively distinguish the atherosclerotic plaque and normal arterial. The expression level of CCRL2, LGALS9, and PLCB2 increases with the accumulation of lipid increased. Conclusion. We identified CCRL2, LGALS9, and PLCB2 as key genes associated with abnormal ESS and AS and may provide potential prevention and treatment target of AS induced by abnormal ESS.

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Galectin-9: A Suppressor of Atherosclerosis?

Cited by 14 publications

References 44 publications

Coexpression of HHLA2 and PD-L1 on Tumor Cells Independently Predicts the Survival of Spinal Chordoma Patients

Coexpression of HHLA2 and PD-L1 on Tumor Cells Independently Predicts the Survival of Spinal Chordoma Patients

Sex differences in coronary artery disease and diabetes revealed by scRNA-Seq and CITE-Seq of human CD4+ T cells

Exploration of the Crucial Genes and Molecular Mechanisms Mediating Atherosclerosis and Abnormal Endothelial Shear Stress

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