Unbalanced expression of membrane-bound and soluble inducible costimulator and programmed cell death 1 in patients with myasthenia gravis

Yan, Xiaoming; Gu, Yanzheng; Wang, Caiqin; Sun, Simao; Wang, Xiaozhu; Tian, Jingluan; Wang, Mingyuan; Ji, Xiaopei; Duan, Xiaoyu; Gao, Hanqing; Fang, Qi; Dong, Wanli; Zhang, Xueguang; Xue, Qun

doi:10.1016/j.clim.2019.07.011

Cited by 14 publications

(11 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…11 A previous study showed that Anlotinib inhibited hepatocellular carcinoma cells via apoptosis induction. 24 In this study as well, Anlotinib significantly induced apoptosis in the KRAS mutant lung cancer cells by downregulating the survival factor BCL-2 and upregulating the pro-apoptotic factor BAX 25,26 in a dose-dependent manner.…”

Section: Discussionsupporting

confidence: 54%

<p>Anlotinib Exerts Anti-Cancer Effects on KRAS-Mutated Lung Cancer Cell Through Suppressing the MEK/ERK Pathway</p>

Liu

Tan

et al. 2020

CMAR

View full text Add to dashboard Cite

Background: With a high frequency of 30%, KRAS mutations in patients with non-small cell lung cancer (NSCLC) often lead to their poor response to most anti-cancer therapies. As a multi-target tyrosine kinase inhibitor, Anlotinib shows clinical efficacy against several types of cancer. However, its effects on KRAS mutant NSCLC and the underlying molecular mechanisms remain unclear. Materials and Methods: Cell counting Kit-8 assay, colony formation assay, flow cytometry analysis, wound healing scratch assay, Transwell assay and xenograft mouse model were used to evaluate the anti-cancer effects of Anlotinib. The potential molecular mechanisms were determined by immunohistochemistry (IHC) and Western blotting. Results: Anlotinib inhibited proliferation of KRAS mutant lung cancer cells and induced apoptosis in vitro. In addition, the migration and invasion abilities of these cells were also decreased after treatment with Anlotinib. It significantly suppressed tumor growth in vivo and prolonged the survival of the xenograft-bearing mice, which correlated to lower expression levels of Ki67 in the tumor tissues. Mechanistically, Anlotinib downregulated MEK and ERK as well as their phosphorylated forms in the KRAS mutant lung cancer cells. Conclusion: Anlotinib inhibits the growth of KRAS mutant lung cancer cells partly via the suppression of the MEK/ERK pathway. Our findings provide novel insights into treating recalcitrant KRAS mutated NSCLC.

show abstract

Section: Discussionsupporting

confidence: 54%

<p>Anlotinib Exerts Anti-Cancer Effects on KRAS-Mutated Lung Cancer Cell Through Suppressing the MEK/ERK Pathway</p>

Liu

Tan

et al. 2020

CMAR

View full text Add to dashboard Cite

show abstract

“…In myasthenia gravis high soluble ICOSLG is suggested to induce peripheral blood follicular helper T (Tfh) cell activation and proliferation. 38 Tfh cell levels in glioma tissue have been found to be negatively related to prognosis 39 and a predictor for malignant transformation from low-grade to high-grade gliomas. 40 Paradoxically, we found high plasma ICOSLG to be associated with long OS in newly diagnosed GBM; ICOSLG expression was not associated with survival in the TCGA GBM dataset; and immune cell deconvolution of TCGA GBM samples revealed that ICOSLG expression was not correlated with regulatory T cells and negatively correlated with the presence of Tfh cells, adding to the complexity of ICOSLG immune regulation.…”

Section: Discussionmentioning

confidence: 99%

Plasma IL-8 and ICOSLG as prognostic biomarkers in glioblastoma

Holst

Christensen

Vitting-Seerup

et al. 2021

Neuro-Oncology Advances

View full text Add to dashboard Cite

Background CNS immune privilege has been challenged in recent years. Glioblastoma (GBM) immune dysfunction includes complex interactions with the immune system outside the CNS. The aim of this study was to determine diagnostic and prognostic potential of immune-related proteins in plasma in GBM and interrogate biomarker presence in the brain tumor microenvironment (TME). Methods 158 patients with glioma WHO grade II–IV were included. Plasma collected at surgery was screened for 92 proteins using proximity extension assay technology and related to clinical outcome. Secretion and expression of candidate prognostic biomarkers were subsequently analyzed in 8 GBM cell lines and public RNAseq data. Results Plasma levels of 20 out of 92 screened proteins were significantly different in patients with GBM compared to patients with astrocytoma WHO grade II–III. High plasma IL-8 (HR=1.52; P=0.0077) and low CD244 (HR=0.36; P=0.0004) were associated with short progression-free survival (PFS) and high plasma IL-8 (HR=1.40; P=0.044) and low ICOS ligand (ICOSLG) (HR=0.17; P=0.0003) were associated with short overall survival (OS) in newly diagnosed patients with GBM. A similar trend was found for ICOSLG (HR=0.34; P=0.053) in recurrent GBM. IL-8 was mostly secreted and expressed by mesenchymal GBM cell lines and expressed by vascular cells and immune cells in the TME. This was also the case for ICOSLG, although less consistent, and with additional expression in tumor-associated oligodendrocytes. Conclusions High plasma IL-8 and low ICOSLG at surgery are associated with short OS in newly diagnosed GBM. Source of plasma ICOSLG may be found outside the TME.

show abstract

“…A decrease of Tfh population with IS treatment has been documented in SLE (33) and also in IgG4-related disease (34). In a recent report, CD4 + PD-1 + and CD4 + ICOS + T cells were decreased after IS treatment in MG as well (45). Soluble forms of PD-1 and ICOSL were also increased in untreated patients and affected by IS treatment.…”

Section: Is Treatment Effectmentioning

confidence: 93%

“…Isotype switching to IgG subclasses as in many autoimmune responses including MG is also subject to regulation by Tfh cells. With the observation of cTfh cells in the blood, several reports are published on the role of these cells in autoimmune diseases such as RA (17), SSc (19), and MG (23,45). In MG, an increase of PD-1 hi CXCR5 + CD4 + or ICOS hi CXCR5 + CD4 + T cell populations and a correlation with AChR antibodies were shown (22).…”

Section: Tfh or Other Cd4 + T Cell Typesmentioning

confidence: 99%

CD4+ T Cells of Myasthenia Gravis Patients Are Characterized by Increased IL-21, IL-4, and IL-17A Productions and Higher Presence of PD-1 and ICOS

et al. 2020

View full text Add to dashboard Cite

Çebi et al. Cytokine and TFH Activity in MG than those in the treated group, whereas the Tfh1 cells were decreased compared with those in the controls. The relevance of CXCR5 and PD-1 in the pathogenesis of AChR-MG was also suggested by the increased presence of these molecules on mature CD4 single-positive thymocytes from the thymic samples. The study provides further evidence for the importance of IL-21, IL-17A, IL-4, and IL-10 in AChR-MG. Disease-related CD4 + T cells are identified mainly as PD-1 + or ICOS + with or without CXCR5, resembling cTfh cells in the circulation or probably in the thymus. AChR-MG and SN-MG seem to have some similar characteristics. IS treatment has distinctive effects on cytokine expression.

show abstract

Unbalanced expression of membrane-bound and soluble inducible costimulator and programmed cell death 1 in patients with myasthenia gravis

Cited by 14 publications

References 34 publications

<p>Anlotinib Exerts Anti-Cancer Effects on KRAS-Mutated Lung Cancer Cell Through Suppressing the MEK/ERK Pathway</p>

<p>Anlotinib Exerts Anti-Cancer Effects on KRAS-Mutated Lung Cancer Cell Through Suppressing the MEK/ERK Pathway</p>

Plasma IL-8 and ICOSLG as prognostic biomarkers in glioblastoma

CD4+ T Cells of Myasthenia Gravis Patients Are Characterized by Increased IL-21, IL-4, and IL-17A Productions and Higher Presence of PD-1 and ICOS

Contact Info

Product

Resources

About