The R132H mutation in <scp>IDH</scp>1 promotes the recruitment of <scp>NK</scp> cells through <scp>CX</scp>3<scp>CL</scp>1/<scp>CX</scp>3<scp>CR</scp>1 chemotaxis and is correlated with a better prognosis in gliomas

Ren, Feifei; Zhao, Qitai; Huang, Lan; Yang, Zheng; Li, Lifeng; He, Qianyi; Zhang, Chaoqi; Li, Feng; Maimela, Nomathamsanqa Resegofetse; Sun, Zhi; Jia, Qingquan; Yü, Ping; Zhang, Zhen; Chen, Xinfeng; Ye, Ying; Li, Shasha; Cao, Liu; Zhang, Yi

doi:10.1111/imcb.12225

Cited by 51 publications

(22 citation statements)

References 54 publications

(84 reference statements)

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“…We found that incubation VMECs with CX3CL1 significantly increased the migration rate of cancer cells and that inhibiting Src/P115-RhoGEF/ROCK signaling in VEMCs effectively blocked the process of tumor cell TEM. These data together with the results of previous studies (Furio et al, 2018;Ren et al, 2019) indicated that in addition to their roles in chemotaxis and adhesion, CX3CL1mediated VMECs barrier disruption and subsequent vertebral micro-vascular hyper-permeability also play key roles in cancer cell TEM in the spine.…”

Section: Discussionsupporting

confidence: 78%

CX3CL1 Induces Vertebral Microvascular Barrier Dysfunction via the Src/P115-RhoGEF/ROCK Signaling Pathway

Lee

Liang

Zhao

et al. 2020

Front. Cell. Neurosci.

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Trans-endothelial migration (TEM) of cancer cells is a critical step in metastasis. Micro-vascular barrier disruptions of distant organs play important roles in tumor cells TEM. The spine is a preferred site for multiple cancer cell metastases. Our previous study found that vertebral spongy bone was rich in CX3CL1 and that CX3CL1 can attract fractalkine receptor-expressing tumor cells to the spine. In the present study, we determined whether CX3CL1 was involved in vertebral micro-vascular barrier disruption and promoted tumor cell TEM after circulating tumor cells were arrested in the vertebral micro-vasculature. We examined the role of CX3CL1 in the barrier function of vertebral micro-vascular endothelial cells (VMECs) and explored the molecular mechanisms of CX3CL1-induced VMEC barrier disruption. Our results demonstrated that CX3CL1 led to F-actin formation and ZO-1 disruption in VMECs and induced the vertebral micro-vascular barrier disruption. Importantly, we found that the activation of the Src/P115-RhoGEF/ROCK signaling pathway plays an important role in CX3CL1-induced VMEC stress fiber formation, ZO-1 disruption and then vertebral micro-vascular barrier hyper-permeability. Inhibiting Src/P115-RhoGEF/ROCK signaling in VMECs effectively blocked CX3CL1-induced vertebral vascular endothelial dysfunction and subsequent tumor cell TEM. The results of this study and our previous study indicate that in addition to its chemotaxis, CX3CL1 plays a critical role in regulating vertebral micro-vascular barrier function and tumor cell TEM. CX3CL1 induced VMECs stress fiber formation, ZO-1 disruption and then vascular endothelial hyperpermeability via activation of the Src/P115-RhoGEF/ROCK signaling pathway. The inhibition of the Src/P115-RhoGEF/ROCK signaling pathway in VMECs effectively blocked tumor cells TEMs in vertebral spongy bone and maybe a potential therapeutic strategy for spine metastases in the future.

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Section: Discussionsupporting

confidence: 78%

CX3CL1 Induces Vertebral Microvascular Barrier Dysfunction via the Src/P115-RhoGEF/ROCK Signaling Pathway

Lee

Liang

Zhao

et al. 2020

Front. Cell. Neurosci.

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“…Several computational-based studies show that glioma patients expressing activated NK cell transcriptional signatures (TS) have improved prognosis (2,(25)(26)(27)(28)(29). Studies in patients and mouse models support these findings (10,30,31), with one human study showing a remarkable relationship between the presence of activated NK cells and improved survival in GBM (32). Another study showed that activated NK cells were higher in low grade compared to high grade gliomas suggesting reduction in activated NK cells is associated with transition from low to high grade brain cancers (27).…”

Section: Nk Cells In Brain Cancermentioning

confidence: 88%

The Role of NK Cells and Innate Lymphoid Cells in Brain Cancer

et al. 2020

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The brain is considered an immune privileged site due to the high selectivity of the blood-brain barrier which restricts the passage of molecules and cells into the brain parenchyma. Recent studies have highlighted active immunosurveillance mechanisms in the brain. Here we review emerging evidence for the contribution of innate lymphoid cells (ILCs) including natural killer (NK) cells to the immunosurveillance of brain cancers focusing on glioblastoma, one of the most aggressive and most common malignant primary brain tumors diagnosed in adults. Moreover, we discuss how the local tissue microenvironment and unique cellular interactions influence ILC functions in the brain and how these interactions might be successfully harnessed for cancer immunotherapy using insights gained from the studies of autoimmunity, aging, and CNS injury.

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“…Sevoflurane was also reported to attenuate NK cell–mediated cytotoxicity by inhibiting adhesion molecule leukocyte function-associated antigen-1 in an experimental study 45 . The importance of NK cells for glioma outcomes has been recently addressed; the IDH1 R132 mutation promotes recruitment of NK cells in the brain and is associated with improved glioma prognosis 46 . In addition, novel therapies based on augmentation of NK cell recruitment and function are emerging in neuro-oncology 47 .…”

Section: Discussionmentioning

confidence: 99%

Influence of scalp block on oncological outcomes of high-grade glioma in adult patients with and without isocitrate dehydrogenase-1 mutation

Sung

Lin

Chan

et al. 2021

Sci Rep

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High-grade gliomas are notorious for a high recurrence rate even after curative resection surgery. Studies regarding the influence of scalp block on high-grade gliomas have been inconclusive, possibly because the condition’s most important genetic mutation profile, namely the isocitrate dehydrogenase 1 (IDH1) mutation, had not been analyzed. Therefore, we conducted a single-center study including patients with high-grade glioma who underwent tumor resection between January 2014 and December 2019. Kaplan–Meier survival analysis revealed that scalp block was associated with longer progression-free survival (PFS; 15.17 vs. 10.77 months, p = 0.0018), as was the IDH1 mutation (37.37 vs. 10.90 months, p = 0.0149). Multivariate Cox regression analysis revealed that scalp block (hazard ratio: 0.436, 95% confidence interval: 0.236–0.807, p = 0.0082), gross total resection (hazard ratio: 0.405, 95% confidence interval: 0.227–0.721, p = 0.0021), and IDH1 mutation (hazard ratio: 0.304, 95% confidence interval: 0.118–0.784, p = 0.0138) were associated with better PFS. Our results demonstrate that application of scalp block, regardless of IDH1 profile, is an independent factor associated with longer PFS for patients with high-grade glioma.

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The R132H mutation in IDH1 promotes the recruitment of NK cells through CX3CL1/CX3CR1 chemotaxis and is correlated with a better prognosis in gliomas

Cited by 51 publications

References 54 publications

CX3CL1 Induces Vertebral Microvascular Barrier Dysfunction via the Src/P115-RhoGEF/ROCK Signaling Pathway

CX3CL1 Induces Vertebral Microvascular Barrier Dysfunction via the Src/P115-RhoGEF/ROCK Signaling Pathway

The Role of NK Cells and Innate Lymphoid Cells in Brain Cancer

Influence of scalp block on oncological outcomes of high-grade glioma in adult patients with and without isocitrate dehydrogenase-1 mutation

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