Hydroxychloroquine sensitizes chronic myeloid leukemia cells to Vγ9Vδ2 T cell-mediated lysis independent of autophagy

Han, Biqing; Zhao, Yanmin; Lin, Yaw Huei; Fu, Shan; Wang, Limengmeng; Zhang, Mingming; Tie, Ruxiu; Wang, Binsheng; Luo, Yi; Liu, Lizhen; Yu, Jian; Huang, He

doi:10.3892/ijo.2017.3934

Cited by 5 publications

(3 citation statements)

References 60 publications

(80 reference statements)

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“…Assessing abundance of ULBP4 transcripts in a broad variety of human tumor cell lines, we detected ULBP4 transcripts most abundantly in the cervix carcinoma cell line HeLa, whereas ULBP4 transcripts were undetectable in liver cancer cells HepG2 or in the erythroleukemia line K562 (Figure 4 B and data not shown) well in line with publicly available data sets. 4 Of note, pronounced ULBP4 surface expression has been claimed based on binding of mAb 709116 for HepG2 cells by the supplier, 5 for the erythroleukemia line K562 ( 42 ) and for cytokine-activated NK cells ( 32 ). By using DUMO1 and ULBP4-specific pAb, we were unable to detect ULBP4 surface expression on HeLa, HepG2, HCT116, and HaCat cells, respectively.…”

Section: Resultsmentioning

confidence: 99%

Cutting an NKG2D Ligand Short: Cellular Processing of the Peculiar Human NKG2D Ligand ULBP4

et al. 2018

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Stress-induced cell surface expression of MHC class I-related glycoproteins of the MIC and ULBP families allows for immune recognition of dangerous “self cells” by human cytotoxic lymphocytes via the NKG2D receptor. With two MIC molecules (MICA and MICB) and six ULBP molecules (ULBP1–6), there are a total of eight human NKG2D ligands (NKG2DL). Since the discovery of the NKG2D–NKG2DL system, the cause for both redundancy and diversity of NKG2DL has been a major and ongoing matter of debate. NKG2DL diversity has been attributed, among others, to the selective pressure by viral immunoevasins, to diverse regulation of expression, to differential tissue expression as well as to variations in receptor interactions. Here, we critically review the current state of knowledge on the poorly studied human NKG2DL ULBP4. Summarizing available facts and previous studies, we picture ULBP4 as a peculiar ULBP family member distinct from other ULBP family members by various aspects. In addition, we provide novel experimental evidence suggesting that cellular processing gives rise to mature ULBP4 glycoproteins different to previous reports. Finally, we report on the proteolytic release of soluble ULBP4 and discuss these results in the light of known mechanisms for generation of soluble NKG2DL.

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Section: Resultsmentioning

confidence: 99%

Cutting an NKG2D Ligand Short: Cellular Processing of the Peculiar Human NKG2D Ligand ULBP4

et al. 2018

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“…It has also been established that Vδ1 and Vδ2 cells can destroy ULBP2 + LCs ( 133 ). Although an almost undetectable ULBP4 expression has been reported in leukemias ( 129 , 134 ), remarkably, it has been shown that Vδ2 cells detect this molecule in LCs and respond with potent cytotoxicity ( 135 ). Therefore, the NKG2D receptor plays a key-role in γδ T cell-mediated immune surveillance in leukemia.…”

Section: γδ T Cells and Leukemia: The Leukemic Microenvironment Mattersmentioning

confidence: 99%

γδ T Cells for Leukemia Immunotherapy: New and Expanding Trends

et al. 2021

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Recently, many discoveries have elucidated the cellular and molecular diversity in the leukemic microenvironment and improved our knowledge regarding their complex nature. This has allowed the development of new therapeutic strategies against leukemia. Advances in biotechnology and the current understanding of T cell-engineering have led to new approaches in this fight, thus improving cell-mediated immune response against cancer. However, most of the investigations focus only on conventional cytotoxic cells, while ignoring the potential of unconventional T cells that until now have been little studied. γδ T cells are a unique lymphocyte subpopulation that has an extensive repertoire of tumor sensing and may have new immunotherapeutic applications in a wide range of tumors. The ability to respond regardless of human leukocyte antigen (HLA) expression, the secretion of antitumor mediators and high functional plasticity are hallmarks of γδ T cells, and are ones that make them a promising alternative in the field of cell therapy. Despite this situation, in particular cases, the leukemic microenvironment can adopt strategies to circumvent the antitumor response of these lymphocytes, causing their exhaustion or polarization to a tumor-promoting phenotype. Intervening in this crosstalk can improve their capabilities and clinical applications and can make them key components in new therapeutic antileukemic approaches. In this review, we highlight several characteristics of γδ T cells and their interactions in leukemia. Furthermore, we explore strategies for maximizing their antitumor functions, aiming to illustrate the findings destined for a better mobilization of γδ T cells against the tumor. Finally, we outline our perspectives on their therapeutic applicability and indicate outstanding issues for future basic and clinical leukemia research, in the hope of contributing to the advancement of studies on γδ T cells in cancer immunotherapy.

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“… 96 , 97 While cancer cells may secrete immunosuppressive mediators to inhibit T cells’ cytotoxicity, both ART and ARS help cancer cells regain sensitivity to γδ T cells via inhibiting TGF-b secretion. 97 , 101 These results suggested that ARTs may help construct a more stressful microenvironment for cancer cells, and its potential application in cancer-related immune regulation is worth of exploring in the future.…”

Section: Immunoregulating Effect Of Antiparasitic Agentsmentioning

confidence: 93%

Progress in Redirecting Antiparasitic Drugs for Cancer Treatment

Huang¹,

He²,

Bing-hua³

et al. 2021

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Drug repurposing is a feasible strategy in developing novel medications. Regarding the cancer field, scientists are continuously making efforts to redirect conventional drugs into cancer treatment. This approach aims at exploring new applications in the existing agents. Antiparasitic medications, including artemisinin derivatives (ARTs), quinine-related compounds, niclosamide, ivermectin, albendazole derivatives, nitazoxanide and pyrimethamine, have been deeply investigated and widely applied in treating various parasitic diseases for a long time. Generally, their pharmacokinetic and pharmacodynamic properties are well understood, while the side effects are roughly acceptable. Scientists noticed that some of these agents have anticancer potentials and explored the underlying mechanisms to achieve drug repurposing. Recent studies show that these agents inhibit cancer progression via multiple interesting ways, inducing ferroptosis induction, autophagy regulation, mitochondrial disturbance, immunoregulation, and metabolic disruption. In this review, we summarize the recent advancement in uncovering antiparasitic drugs’ anticancer properties from the perspective of their pharmacological targets. Instead of paying attention to the previously discovered mechanisms, we focus more on newly emerging ones that are worth noticing. While most investigations are focusing on the mechanisms of their antiparasitic effect, more in vivo exploration in clinical trials in the future is necessary. Moreover, we also paid attention to what limits the clinical application of these agents. For some of these agents like ARTs and niclosamide, drug modification, novel delivery system invention, or drug combination are strongly recommended for future exploration.

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Hydroxychloroquine sensitizes chronic myeloid leukemia cells to Vγ9Vδ2 T cell-mediated lysis independent of autophagy

Cited by 5 publications

References 60 publications

Cutting an NKG2D Ligand Short: Cellular Processing of the Peculiar Human NKG2D Ligand ULBP4

Cutting an NKG2D Ligand Short: Cellular Processing of the Peculiar Human NKG2D Ligand ULBP4

γδ T Cells for Leukemia Immunotherapy: New and Expanding Trends

Progress in Redirecting Antiparasitic Drugs for Cancer Treatment

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