Selenium nanoparticles as new strategy to potentiate γδ T cell anti-tumor cytotoxicity through upregulation of tubulin-α acetylation

Hu, Yi; Liu, Ting; Li, Jingxia; Mai, Feng-Yi; Li, Jiawei; Chen, Yan; Jing, Yan-Yun; Dong, Xin; Li, Lin; He, Junyi; Xu, Yan; Shan, Changliang; Hao, Jianlei; Yin, Zhinan; Chen, Tianfeng; Wu, Yangzhe

doi:10.1016/j.biomaterials.2019.119397

Cited by 83 publications

(58 citation statements)

References 46 publications

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“…This finding was consistent with the previous report by Alnaggar et al 28 In addition to increase of lymphocytes, the levels of IL-2, IFN-γ, and TNF-β were also improved, suggesting a stronger antitumor efficacy. 20 As we all know, NKG2D plays an important role in identifying and killing tumor, IRE plus γδ T cells could markedly upregulated NKG2D. Similarly, PD-1 of γδ T cells was markedly downregulated after IRE plus γδ T-cell therapy.…”

Section: Discussionmentioning

confidence: 92%

“…4,19 In recent years, immune cell therapy has been applied more and more to tumor therapy. 20,21 In TME, T cells are a key component, and treatment with ICIs or adoptive cell infusion has led to breakthroughs in cancer therapy. 22 Most clinical application of T cells was centered on αβ T cells (CD4 + , CD8 + T cells), γδ T cells are also important players in cancer immunity.…”

Section: Introductionmentioning

confidence: 99%

“…The human γδ T cells can be activated in a major histocompatibility complex (MHC)-independent manner, which makes it broader antitumor cytotoxicity. 20 The Vγ9Vδ2 T cell is an important component of immune effector cells that contribute to tumor immune-surveillance against many types of tumors, [24][25][26][27] which indicates that the Vγ9Vδ2-T cell can be used as a promising candidate treatment for LAPC. But up to now, there is only one case report on γδ T cells in cholangiocarcinoma patient, 28 it demonstrated that allogenic γδ T-cell treatments positively enhanced immune functions, depleted tumor activity, improved quality of life (QOL), and prolonged survival.…”

Section: Introductionmentioning

confidence: 99%

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Irreversible electroporation plus allogenic Vγ9Vδ2 T cells enhances antitumor effect for locally advanced pancreatic cancer patients

Lin

Zhang

Liang

et al. 2020

Sig Transduct Target Ther

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Immunotherapy has limited efficacy against locally advanced pancreatic cancer (LAPC) due to the presence of an immunosuppressive microenvironment (ISM). Irreversible electroporation (IRE) can not only induce immunogenic cell death, but also alleviate immunosuppression. This study aimed to investigate the antitumor efficacy of IRE plus allogeneic γδ T cells in LAPC patients. A total of 62 patients who met the eligibility criteria were enrolled in this trial, then randomized into two groups (A: n = 30 and B: n = 32). All patients received IRE therapy and after receiving IRE, the group A patients received at least two cycles of γδ T-cell infusion as one course continuously. Group A patients had better survival than group B patients (median OS: 14.5 months vs. 11 months; median PFS: 11 months vs. 8.5 months). Moreover, the group A patients treated with multiple courses of γδ T-cell infusion had longer OS (17 months) than those who received a single course (13.5 months). IRE combined with allogeneic γδ T-cell infusion is a promising strategy to enhance the antitumor efficacy in LAPC patients, yielding extended survival benefits. ClinicalTrials.gov ID: NCT03180437.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Irreversible electroporation plus allogenic Vγ9Vδ2 T cells enhances antitumor effect for locally advanced pancreatic cancer patients

Lin

Zhang

Liang

et al. 2020

Sig Transduct Target Ther

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“…The methodology of γδ T cell isolation and culture had been described in detail in previous reports [14,27,28]. Briefly, the isolated peripheral blood monocyte cells (PBMCs) using Ficoll-Paque centrifuge from healthy volunteers were cultured in RPMI-1640 culture medium supplemented with 10% fetal bovine serum (FBS), IL-2 (5ng/ml) and zoledronate (10 nM); then cells were seeded into 24 or 48 well-plates.…”

Section: Materials and Methods γδ T Cell Isolation And Culturementioning

confidence: 99%

Vγ9Vδ2 T Cells Strengthen Cisplatin Inhibition Activity Against Breast Cancer MDA-MB-231 Cells by Destructing Mitochondrial Function and Cell Ultrastructure

Huang

Wang

2020

Preprint

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Background: Breast cancer ranks second of new cases and fifth of death in 2018 world widely. Chemotherapy, one of cancer therapeutic strategies, plays important role in controlling mortality of breast cancer. Cis-platinum (CDDP), one of traditional chemotherapy drugs, had been used clinically for years. The crucial limitation of CDDP is due to its adverse effects on immune system. Development of new protocol that can minimize side effect and meanwhile elevate clinical efficacy of traditional drug like CDDP will eventually benefit cancer patients. Vγ9Vδ2 T cells had been reported to be able to up-regulate immune function of cancer patients, therefore, our hypothesis is that introduction of Vγ9Vδ2 T cells could potentiate CDDP efficacy against breast cancer. Methods: In the present work, breast cancer cell line MDA-MB-231 was used a model cell to test our hypothesis. The therapeutic dose of CDDP in vitro was analyzed by flow cytometry; The cytoskeleton was visualized by using a confocal microscopy, and the ultrastructure of the membrane was observed by atomic force microscopy to observe the effect of combined action on MDA-MB-231 cells; The mitochondrial function of MDA-MB-231 cells was detected, and the relevant mechanism of Vγ9Vδ2 T in enhancing cisplatin cells' inhibition of MDA-MB-231 cells was discussed. Results: Vγ9Vδ2 T cells could enhance CDDP-induced MDA-MB-231 cell membrane ultrastructure disorder and cytoskeleton disorder, and enhance the inhibition of CDDP on MDA-MB-231 cells, of which Vγ9Vδ2 T cells enhancing CDDP-induced mitochondrial dysfunction was one of its mechanisms. Conclusion: In this study，the mechanism of Vγ9Vδ2 T cells in enhancing the inhibition of cisplatin on MDA-MB-231 cells was studied, which could provide an important scientific clue for developing effective treatment schemes for breast cancer, especially the refractory TNBC breast cancer, based on Vγ9Vδ2 T cells in the future.

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“…Tube number and branch points were statistically analyzed using ImageJ software. [14] Western Blot analysis To test expressions of functional proteins, Western Blot was used here by following the standard protocols of our lab [25] . HUVECs (5 × 10 6 ) were pre-treated with MSCs-exo (5 × 10 9 ) after 24 hours.…”

Section: In Vitro Cellular Proliferation Assaymentioning

confidence: 99%

Human Mesenchymal Stem Cells Promote Ischemic Repairment and Angiogenesis of Diabetic Foot Through Exosome miRNA-21-5p

Huang

Luo

Wang³

et al. 2020

Preprint

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Background: Diabetic foot is caused by ischemic disease of lower extremities of diabetic patients, and the effective therapy is very limited. Mesenchymal stem cells (MSCs) based cell therapy had been developed into a new treatment strategy for diabetic foot clinically. However, the underlying molecular mechanism remains to be fully addressed. Exosomes secreted by MSCs may play crucial role in the processes of MSCs mediated inhibition of inflammatory microenvironment as well as pro-angiogenesis of ischemic tissue of diabetic foot. Methods: Exosomes were isolated from MSCs using ultra-high centrifugation, and further characterized by the nanoparticle tracking analyzer and flow cytometry. Moreover, RNA sequencing, Western Blot, in vitro cell proliferation, in vivo pro-angiogenesis, as well as ischemic repairment of diabetic foot through rat model were performed to evaluate exosome physiological functions. Results: We found that different inflammatory cytokines (tumor necrosis factor a, vascular cell adhesion molecule-1 and interleukin-6) induced MSCs to secrete exosomes heterogeneously, including exosome size and quantity. Through RNA sequencing, we defined a new proangiogenic miRNA, miRNA-21-5p. Further knockdown and overexpression of miRNA-21-5p by manipulating MSCs validated the biological activity of exosome miRNA-21-5p, including in vitro cell proliferation, in vivo pro-angiogenesis in Chick Chorioallantoic Membrane (CAM) assay, and in vivo pro-angiogenesis experiments (tissue injury and repair) in diabetic rat models. Furthermore, we discovered that exosomemiRNA-21-5p promoted angiogenesis through upregulations of vascular endothelial growth factor receptor (VEGFR) as well as activations of serine/threonine kinase (AKT) and mitogen-activated protein kinase (MAPK). Together, our work suggested miRNA-21-5p could be a novel mechanism by which exosomes promote ischemic tissue repairing and angiogenesis. Meanwhile, miRNA-21-5p could be potentially developed into a new biomarker for exosomes of MSCs to treat diabetic foot. Conclusions: miRNA-21-5p is a new biomarker and a novel mechanism by which exosomes promote ischemic tissue repairing and angiogenesis of diabetic foot. Our work could not only provide new scientific evidences for revealing pro-angiogenesis mechanism of MSCs, but also eventually benefit MSCs-based clinical therapy for diabetic foot of diabetes patients.

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Selenium nanoparticles as new strategy to potentiate γδ T cell anti-tumor cytotoxicity through upregulation of tubulin-α acetylation

Cited by 83 publications

References 46 publications

Irreversible electroporation plus allogenic Vγ9Vδ2 T cells enhances antitumor effect for locally advanced pancreatic cancer patients

Irreversible electroporation plus allogenic Vγ9Vδ2 T cells enhances antitumor effect for locally advanced pancreatic cancer patients

Vγ9Vδ2 T Cells Strengthen Cisplatin Inhibition Activity Against Breast Cancer MDA-MB-231 Cells by Destructing Mitochondrial Function and Cell Ultrastructure

Human Mesenchymal Stem Cells Promote Ischemic Repairment and Angiogenesis of Diabetic Foot Through Exosome miRNA-21-5p

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