Functions of NKG2D in CD8+ T cells: an opportunity for immunotherapy

Prajapati, Kushal; Pérez, Cynthia; Rojas, Lourdes Beatriz Plaza; Burke, Brianna; Guevara-Patiño, José A.

doi:10.1038/cmi.2017.161

Cited by 101 publications

(96 citation statements)

References 84 publications

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“…Consequent the binding of ligands, NKG2D receptor can initiate an intracellular signal cascade that leads to NK and NKT activation ( 18 ). Conversely in T cells the function of NKG2D receptor is different acting as a co-stimulatory molecule enhancing T-cell receptor activation (TCR) and T cells functions ( 19 ). In human beings some polymorphisms in MICA gene have been documented.…”

Section: Discussionmentioning

confidence: 99%

Higher Frequencies of Lymphocytes Expressing the Natural Killer Group 2D Receptor in Patients With Behçet Disease

et al. 2018

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Behçet disease (BD) is an inflammatory systemic disease with a fluctuating course, which can affect the skin, eyes, central nervous system, musculoskeletal, gastrointestinal, and vascular systems. No laboratory tests are currently available for the diagnosis of BD and monitoring disease activity. Moreover there is a lack of knowledge on BD pathogenesis. This study focused on circulating Natural Killer (NK), NKT and T cells evaluated as CD3neg CD56pos, CD3pos CD56pos, and CD3pos CD56neg. Peripheral blood mononuclear cells (PBMCs) were collected from 38 BD patients and 20 healthy controls (HC). The frequencies of NK, NKT, and T cells expressing CD16, CD69, NKG2D, Nkp30, Nkp46, and NKG2A were assessed by flow cytometry. Cytotoxic potential of NK cells was evaluated by flow cytometry as the percentage of cells expressing the degranulation marker CD107a after incubation with K562 cells. The levels of 27 cytokines were determined in plasma with a multiplex bead-based assay. Higher percentages of NK, NKT, and T cells expressing NKG2D were detected in PBMCs of BD patients than HC. ROC curve analysis showed that the evaluation of NKG2Dpos NK, NKT, and T cell percentages discriminated between BD patients and HC. Moreover, there was a positive correlation between the BD Current Activity Form (BDCAF) scores and the frequencies of NKG2Dpos NK and NKT cells. A higher frequency of NK cells expressing CD107a was induced in PBMCs from BD patients than HC after incubation with K562 cells. Concentrations of IL-5, IL-6, IL-10, IL-13, IP-10, and MIP-1β were higher in plasma of BD patients than HC. Monitoring the frequencies of NKG2Dpos lymphocytes could help the clinicians in BD patients management. In addition, the increased expression of NKG2D in BD patients is likely involved in disease pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Higher Frequencies of Lymphocytes Expressing the Natural Killer Group 2D Receptor in Patients With Behçet Disease

et al. 2018

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“…The NKG2D receptor is, in several aspects, an outstanding immune receptor of major interest in research and immunotherapy: First, the NKG2D receptor is expressed on lymphocytes both of the innate immune system, Natural Killer (NK) cells, as well as cytotoxic, CD4 or γδ T cells, which are assigned to the adaptive branch of the immune system ( 1 , 2 ). Being considered a genuine activating receptor on NK cells, NKG2D acts as a co-stimulatory receptor on T cells ( 1 , 3 ). Thereby, NKG2D receptor triggering induces not only cytotoxicity ( 4 ), but also drives cytokine production ( 5 – 7 ), or impacts T cell differentiation and expansion ( 8 , 9 ).…”

Section: The Family Of Stress-induced Ligands Comprises High Diversitmentioning

confidence: 99%

NKG2D Ligands–Critical Targets for Cancer Immune Escape and Therapy

2018

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DNA damage, oncogene activation and excessive proliferation, chromatin modulations or oxidative stress are all important hallmarks of cancer. Interestingly, all of these abnormalities also induce a cellular stress response. By upregulating “stress-induced ligands,” damaged or transformed cells can be recognized by immune cells and cleared. The human genome encodes eight functional “stress-induced ligands”: MICA, MICB, and ULBP1-6. All of them are recognized by a single receptor, NKG2D, which is expressed on natural killer (NK) cells, cytotoxic T cells and other T cell subsets. The NKG2D ligand/NKG2D-axis is well-recognized as an important mediator of anti-tumor activity; however, patient data about the role of NKG2D ligands in immune surveillance and escape appears conflicting. As these ligands are often actively transcribed, tumor cells are urged to manipulate the expression of these ligands on post-transcriptional or post-translational level. Although our knowledge on the regulation of NKG2D ligand expression remains fragmentary, research of the past years revealed multiple cellular mechanisms that are adopted by tumor cells to reduce the expression of “stress-induced ligands” and therefore escape immune recognition. Here, we review the post-transcriptional and post-translational mechanisms by which NKG2D ligands are modulated in cancer cells and their impact on patient prognosis.We discuss controversies and approaches to apply our understanding of the NKG2D ligand/NKG2D-axis for cancer therapy.

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“…The study has so far confirmed the capacity of Dex to boost the NK cell arm of antitumor immunity in patients with advanced NSCLC [116]. A Phase I clinical trial using DEX to treat advanced melanoma illustrated that Dex treatment enhanced the proportion and absolute number of circulating NK cells and restored the expression of a type II transmembrane receptor Natural Killer Group 2 member D (NKG2D), which is expressed on circulating T and NK cells [117], thus stimulating the MHC unrestricted NKG2D dependent cytotoxicity. These data provide a mechanistic explanation on how Dex may stimulate non-MHC restricted-anti-tumor effectors and induce tumor regression in vivo [118].…”

Section: Clinical Trials To Date Using Exosome As a Therapymentioning

confidence: 81%

Exosomes Could Offer New Options to Combat the Long-Term Complications Inflicted by Gestational Diabetes Mellitus

Floriano

Willis

Catapano

et al. 2020

Cells

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Gestational diabetes Mellitus (GDM) is a complex clinical condition that promotes pelvic floor myopathy, thus predisposing sufferers to urinary incontinence (UI). GDM usually regresses after birth. Nonetheless, a GDM history is associated with higher risk of subsequently developing type 2 diabetes, cardiovascular diseases (CVD) and UI. Some aspects of the pathophysiology of GDM remain unclear and the associated pathologies (outcomes) are poorly addressed, simultaneously raising public health costs and diminishing women’s quality of life. Exosomes are small extracellular vesicles produced and actively secreted by cells as part of their intercellular communication system. Exosomes are heterogenous in their cargo and depending on the cell sources and environment, they can mediate both pathogenetic and therapeutic functions. With the advancement in knowledge of exosomes, new perspectives have emerged to support the mechanistic understanding, prediction/diagnosis and ultimately, treatment of the post-GMD outcomes. Here, we will review recent advances in knowledge of the role of exosomes in GDM and related areas and discuss the possibilities for translating exosomes as therapeutic agents in the GDM clinical setting.

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Functions of NKG2D in CD8+ T cells: an opportunity for immunotherapy

Cited by 101 publications

References 84 publications

Higher Frequencies of Lymphocytes Expressing the Natural Killer Group 2D Receptor in Patients With Behçet Disease

Higher Frequencies of Lymphocytes Expressing the Natural Killer Group 2D Receptor in Patients With Behçet Disease

NKG2D Ligands–Critical Targets for Cancer Immune Escape and Therapy

Exosomes Could Offer New Options to Combat the Long-Term Complications Inflicted by Gestational Diabetes Mellitus

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