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更新于：2025-05-07

THBS1 x IFNγ

更新于：2025-05-07

基本信息

关联

项与 THBS1 x IFNγ 相关的药物

TAX-2

靶点

IFNγ x THBS1

作用机制

IFNγ刺激剂 [+3]

在研机构

Apmonia Therapeutics SAS

原研机构

Centre National de la Recherche Scientifique [+1]

在研适应症

结直肠癌 [+4]

非在研适应症-

最高研发阶段临床1/2期

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 THBS1 x IFNγ 相关的临床结果

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100 项与 THBS1 x IFNγ 相关的转化医学

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0 项与 THBS1 x IFNγ 相关的专利（医药）

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项与 THBS1 x IFNγ 相关的文献（医药）

2025-06-01·Experimental Eye Research

Chronic intermittent hypoxia modulates corneal fibrotic markers and inflammatory cytokine expression in a sex-dependent manner

Article

作者: Cunningham, Rebecca L ; Wilson, E Nicole ; Gardner, Jennifer J ; Bradshaw, Jessica L ; Mabry, Steve ; Karamichos, Dimitrios ; Vasini, Brenda ; Hefley, Brenna S

Chronic intermittent hypoxia (CIH) is a commonly observed condition in patients suffering from obstructive sleep apnea (OSA). Previous studies link CIH to fibrosis, inflammation, and hormonal dysregulation across various tissues. Yet, the effect of CIH in the cornea is unknown. Moreover, women and men diagnosed with OSA present with diverse symptoms, suggesting sex-specific pathophysiology at play. Thus, we used a rat model to assess the impact of CIH and sex on protein expression of corneal fibrotic markers (α-SMA, COL III, cFN, TSP-1), proinflammatory cytokines (IL-1 α, IL-17, IL-18, and IFN-γ), and hormone receptors (ERα, ERβ, GPER, GnRH-R, and LH-R). Male and female Sprague Dawley rats were exposed to normoxic or CIH conditions during their sleep cycle for 14 days. Extracted corneal proteins were subjected to Western blot and multiplex magnetic bead analysis. Our results reveal sex differences in fibrotic and inflammatory markers in the cornea, whereby female corneas exhibit higher levels of fibrotic markers, while male corneas exhibit increased inflammatory cytokines. CIH exposure resulted in elevated levels of α-SMA and pro-inflammatory cytokines in female corneas, while there was no impact on fibrotic or inflammatory markers in male corneas. Additionally, CIH exposure reduced hormone receptors in male and female corneas in a sex-dependent manner. Correlation analyses identified associations of corneal hormone receptors with corneal fibrotic and pro-inflammatory markers that were dependent on sex, with female corneas demonstrating stronger correlations compared to male corneas. Altogether, our data suggests hormone-mediated signaling may contribute to CIH-mediated corneal fibrosis and inflammatory phenotypes, especially in females.

2023-11-01·Cancer Letters

Gastric cancer derived exosomal THBS1 enhanced Vγ9Vδ2 T-cell function through activating RIG-I-like receptor signaling pathway in a N6-methyladenosine methylation dependent manner

Article

作者: Li, Juntao ; Zhu, Jinghan ; Zhang, Guangbo ; Gu, Yanzheng ; Chen, Weichang ; Feng, Huang ; Yang, Kexi ; Shi, Tongguo

Gamma delta (γδ) T-cell-based immunotherapy has shown favorable safety and clinical response in patients with multiple types of cancer. However, its efficiency in treating patients with solid tumors remains limited. In the current study, we investigated the function and molecular mechanism underlying gastric cancer (GC) cell-derived exosomal THBS1 in the regulation of Vγ9Vδ2 T cells. We found that GC cell-derived exosomal THBS1 markedly enhanced the cytotoxicity of Vγ9Vδ2 T cells against GC cells and the production of IFN-γ, TNF-α, perforin and granzyme B in vitro and elevated the killing effects of Vγ9Vδ2 T cells on GC cells in vivo. Mechanistically, exosomal THBS1 could regulate METTL3-or IGF2BP2-mediated m6A modification, further activating the RIG-I-like receptor signaling pathway in Vγ9Vδ2 T cells. Moreover, blocking the RIG-I-like receptor signaling pathway reversed the effects of exosomal THBS1 on the function of Vγ9Vδ2 T cells. In addition, THBS1 was expressed at low levels in GC tissues and was associated with an unfavorable prognosis in GC patients. In sum, our findings indicate that exosomal THBS1 derived from GC cells enhanced the function of Vγ9Vδ2 T cells by activating the RIG-I-like signaling pathway in a m6A methylation-dependent manner. Targeting the exosomal THBS1/m6A/RIG-I axis may have important implications for GC immunotherapy based on Vγ9Vδ2 T cells.

2023-09-22·Medicine

Identification of immune microenvironment changes, immune-related pathways and genes in male androgenetic alopecia

Article

作者: Wen, Si-Jian ; Xiong, Hong-Di ; Li, Wen-Yu ; Chen, Hai-Ju ; Tang, Lu-Lu ; Wu, Yi ; Lin, You-Kun

Background:Although androgenetic alopecia (AGA) is classified as a non-inflammatory alopecia, histological evidence of microinflammation has long been recognized. However, changes in the immune microenvironment, immune-related pathways and the expression of immune-related genes (IRGs) involved in AGA remain unclear.Methods:The microarray gene expression data (GSE36169) from patients with male AGA were analyzed. gene set enrichment analysis (GSEA) among statistically changed genes was done. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses among differentially expressed genes were performed. differentially expressed genes were screened to identify IRGs based on the ImmPort database. The cytohubba-MCC plugin of Cytoscape was applied to screen hub immune genes. The infiltration levels of 28 immune cells were quantified adopting single-sample GSEA (ssGSEA) algorithm. The microarray gene expression data (GSE90594) of male AGA was analyzed to validate hub IRGs genes and differential infiltrated immune cells.Results:The ssGSEA revealed γδT cell, central memory CD8+ T cell, mast cell, immature B cell, activated CD8+ T cell, effector memory CD4+ T cell, eosinophil and neutrophil were significantly increased infiltration in the bald scalp. GSEA showed statistically changed genes were most enriched in immune related pathways, including innate immune system, adaptive immune system, cytokine signaling, interferon-γ signaling, interferon signaling and interleukins signaling. The 4 hub IRGs, including matrix metallopeptidase 9, protein tyrosine phosphatase receptor type C, bone morphogenetic protein 2, and thrombospondin 1, were enriched in the pathways of allograft rejection, coagulation and interferon-γ response.Conclusion:In summary, we proposed that the increase in γδ T cells, central memory CD8+ T cells, activated CD8+ T cell as well as the infiltration of mast cells contributed to immune microenvironment changes in male AGA. The 4 hub IRGs may be involved in the development and progression of hair loss in male AGA through interferon-γ signal pathways.

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