Profiling the pattern of the human T-cell receptor γδ complementary determinant region 3 repertoire in patients with lung carcinoma via high-throughput sequencing analysis

Chen, Hui; Zou, Mingjin; Teng, Da; Hu, Yu; Zhang, Jianmin; Wang, He

doi:10.1038/cmi.2017.157

Cited by 16 publications

(11 citation statements)

References 25 publications

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“… 88 Some studies have also noted different γδ TCR repertoires in the blood of cancer patients than in healthy controls. 89 However, to better understand the significance of clonal γδ T cell recruitment to the tumor site, more equivalent studies in various tumors and lymphomas are needed.…”

Section: Tumor-infiltrating γδ T Cells: Friends or Foes?mentioning

confidence: 99%

Cancer immunotherapy with γδ T cells: many paths ahead of us

et al. 2020

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γδ T cells play uniquely important roles in stress surveillance and immunity for infections and carcinogenesis. Human γδ T cells recognize and kill transformed cells independently of human leukocyte antigen (HLA) restriction, which is an essential feature of conventional αβ T cells. Vγ9Vδ2 γδ T cells, which prevail in the peripheral blood of healthy adults, are activated by microbial or endogenous tumor-derived pyrophosphates by a mechanism dependent on butyrophilin molecules. γδ T cells expressing other T cell receptor variable genes, notably Vδ1, are more abundant in mucosal tissue. In addition to the T cell receptor, γδ T cells usually express activating natural killer (NK) receptors, such as NKp30, NKp44, or NKG2D which binds to stress-inducible surface molecules that are absent on healthy cells but are frequently expressed on malignant cells. Therefore, γδ T cells are endowed with at least two independent recognition systems to sense tumor cells and to initiate anticancer effector mechanisms, including cytokine production and cytotoxicity. In view of their HLA-independent potent antitumor activity, there has been increasing interest in translating the unique potential of γδ T cells into innovative cellular cancer immunotherapies. Here, we discuss recent developments to enhance the efficacy of γδ T cell-based immunotherapy. This includes strategies for in vivo activation and tumor-targeting of γδ T cells, the optimization of in vitro expansion protocols, and the development of gene-modified γδ T cells. It is equally important to consider potential synergisms with other therapeutic strategies, notably checkpoint inhibitors, chemotherapy, or the (local) activation of innate immunity.

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Section: Tumor-infiltrating γδ T Cells: Friends or Foes?mentioning

confidence: 99%

Cancer immunotherapy with γδ T cells: many paths ahead of us

et al. 2020

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“…Enhancing the quantity and quality of γδ T cells will be very favorable for their use in further adoptive immunotherapy strategies. 51…”

Section: Discussionmentioning

confidence: 99%

miR-125b-5p and miR-99a-5p downregulate human γδ T-cell activation and cytotoxicity

Zhu

Zhang

et al. 2018

Cell Mol Immunol

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As an important component of innate immunity, human circulating γδ T cells function in rapid responses to infections and tumorigenesis. MicroRNAs (miRNAs) play a critical regulatory role in multiple biological processes and diseases. Therefore, how the functions of circulating human γδ T cells are regulated by miRNAs merits investigation. In this study, we profiled the miRNA expression patterns in human peripheral γδ T cells from 21 healthy donors and identified 14 miRNAs that were differentially expressed between peripheral αβ T cells and γδ T cells. Of the 14 identified genes, 7 miRNAs were downregulated, including miR-150-5p, miR-450a-5p, miR-193b-3p, miR-365a-3p, miR-31-5p, miR-125b-5p and miR-99a-5p, whereas the other 7 miRNAs were upregulated, including miR-34a-5p, miR-16-5p, miR-15b-5p, miR-24-3p, miR-22-3p, miR-22-5p and miR-9-5p, in γδ T cells compared with αβ T cells. In subsequent functional studies, we found that both miR-125b-5p and miR-99a-5p downregulated γδ T cell activation and cytotoxicity to tumor cells. Overexpression of miR-125b-5p or miR-99a-5p in γδ T cells inhibited γδ T cell activation and promoted γδ T cell apoptosis. Additionally, miR-125b-5p knockdown facilitated the cytotoxicity of γδ T cells toward tumor cells in vitro by increasing degranulation and secretion of IFN-γ and TNF-α. Our findings improve the understanding of the regulatory functions of miRNAs in γδ T cell activation and cytotoxicity, which has implications for interventional approaches to γδ T cell-mediated cancer therapy.Cellular and Molecular Immunology advance online publication, 12 February 2018; doi:10.1038/cmi.2017.164.

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“…Speci c T cells were selectively recruited by human Ad-MSCs after transplantation Comprehensive analysis of the TCR or immunoglobulin repertoire by high-throughput sequencing can be used to assess the enrichment of antigen-speci c T cell or B cell clones in many diseases or the immunogenicity of speci c antigens [29,37]. It may also provide clues for elucidating the underlying mechanisms of antitumor immunity in speci c tumors [38]. In this study, we analyzed the TCR repertoire of human Ad-MSC-recruited T cells with the aim of nding dominant TCR clones that respond to human Ad-MSCs.…”

Section: Human Ad-mscs Stimulate the Proliferation And Activation Of mentioning

confidence: 99%

Identification of Potential Immunogenic Molecules During the Allogeneic Transplantation of Human Adipose-derived Mesenchymal Stem Cells

Wang

Fan

et al. 2020

Preprint

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Background: Given their low immunogenicity and multiple differentiation capacities, mesenchymal stem cells (MSCs) have the potential to be used for “off-the-shelf” cell therapy. However, MSC allorejection indicates that they are not fully immune privileged. In this study, we investigated the immunogenicity of human adipose-derived MSCs (Ad-MSCs) and identified potential immunogenic molecules.Methods: To evaluate the immunogenicity of human Ad-MSCs in vivo, cells were transplanted into humanized mice (hu-mice), and T cell infiltration and clearance of human Ad-MSCs were observed by immunofluorescence and bioluminescence imaging. One-way mixed lymphocyte reaction (MLR) and flow cytometry were performed to evaluate the immunogenicity of human Ad-MSCs in vitro. High-throughput TCR repertoire sequencing and mass spectrometry were applied to identify potential immunogenic molecules.Results: Allogeneic human Ad-MSCs recruited T cells during transplantation and caused faster clearance in hu-mice than NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt (NSG) mice. The proliferation and activation of T cells was significantly enhanced by human Ad-MSCs, and the expression level of HLA-II on human Ad-MSCs was dramatically increased after coculture with human peripheral blood mononuclear cells (PBMCs) in vitro. In addition, upregulated expression of alpha-enolase (ENO1) on the surface of human Ad-MSCs increased their immunogenicity, and ENO1 inhibitor treatment decreased the human Ad-MSC triggered proliferation of T cells in vitro.Conclusions: We further confirmed the immunogenicity of human Ad-MSCs during allogeneic transplantation and provided a potential target, ENO1, for the safe clinical application of allogeneic human Ad-MSC therapy.

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Profiling the pattern of the human T-cell receptor γδ complementary determinant region 3 repertoire in patients with lung carcinoma via high-throughput sequencing analysis

Cited by 16 publications

References 25 publications

Cancer immunotherapy with γδ T cells: many paths ahead of us

Cancer immunotherapy with γδ T cells: many paths ahead of us

miR-125b-5p and miR-99a-5p downregulate human γδ T-cell activation and cytotoxicity

Identification of Potential Immunogenic Molecules During the Allogeneic Transplantation of Human Adipose-derived Mesenchymal Stem Cells

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