The inhibitory receptor Tim-3 fails to suppress IFN-γ production via the NFAT pathway in NK-cell, unlike that in CD4+ T cells

Yu, Xiaowen; Lang, Bin; Chen, Xi; Tian, Yuan; Qian, Shi; Zhang, Zining; Fu, Yajing; Xu, Junjie; Han, Xiaoxu; Ding, Haibo; Jiang, Yongjun

doi:10.1186/s12865-021-00417-9

Cited by 9 publications

(11 citation statements)

References 28 publications

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“…Lisovsky et al reported that blockade of NKG2A in vitro increases CD56 dim NKG2A pos NK cell degranulation and secretion of IFN-g and CCL4 against infected CD4 T cells (120). As mentioned in Section Surface Receptor Imbalance Weakens NK Cell Functions blockade of immune checkpoints such as Siglec-9, TIGIT, PD-1, and Tim-3 also enhance the killing activity of NK cells in HIV infection (28,38,44,49). Inhibitors of NK cell inhibitory receptors might thus prove useful for promoting NK cell functions in HIV infection.…”

Section: Blocking Inhibitory Receptors For Nk Cell Functionmentioning

confidence: 97%

“…Yu et al. reported reduced Tim-3 expression on NK cells in HIV-infected individuals ( 49 ), and de Kivit et al. reported reduced Tim-3 expression on NK cells in HIV immunologic non-responders compared with immunologic responders.…”

Section: Nk Cell Dysfunction During Hiv Infectionmentioning

confidence: 99%

“…reported that Tim-3 expression is negatively correlated with levels of IFN-γ secreted by NK cells after ART ( 51 ). Tim-3 pos NK cells suppress NF-κB and ERK phosphorylation to reduce IFN-γ production, and Tim-3 blockade induces NK cells to secrete CD107a ( 49 ). Plasma levels of the Tim-3 ligand, Gal-9, significantly increase during primary HIV infection, and soluble Gal-9 triggers the downregulation of Tim-3 expression ( 52 ).…”

Section: Nk Cell Dysfunction During Hiv Infectionmentioning

confidence: 99%

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Negative Regulation and Protective Function of Natural Killer Cells in HIV Infection: Two Sides of a Coin

2022

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Natural killer (NK) cells play an important immunologic role, targeting tumors and virus-infected cells; however, NK cells do not impede the progression of human immunodeficiency virus (HIV) infection. In HIV infection, NK cells exhibit impaired functions and negatively regulate other immune cell responses, although NK cells can kill HIV-infected cells and thereby suppress HIV replication. Considerable recent research has emerged regarding NK cells in the areas of immune checkpoints, negative regulation, antibody-dependent cell-mediated cytotoxicity and HIV reservoirs during HIV infection; however, no overall summary of these factors is available. This review focuses on several important aspects of NK cells in relation to HIV infection, including changes in NK cell count, subpopulations, and immune checkpoints, as well as abnormalities in NK cell functions and NK cell negative regulation. The protective function of NK cells in inhibiting HIV replication to reduce the viral reservoir and approaches for enhancing NK cell functions are also summarized.

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Section: Blocking Inhibitory Receptors For Nk Cell Functionmentioning

confidence: 97%

Section: Nk Cell Dysfunction During Hiv Infectionmentioning

confidence: 99%

Section: Nk Cell Dysfunction During Hiv Infectionmentioning

confidence: 99%

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Negative Regulation and Protective Function of Natural Killer Cells in HIV Infection: Two Sides of a Coin

2022

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“…Although TIM-3 is a marker of T cell exhaustion ( 153 ), its expression is not associated with NK cell dysfunction in healthy donors. TIM-3 is also expressed in NK cells, the cytolytic activity of TIM-3 + NK cells from healthy humans is higher than that of TIM-3 - NK cells, and the TIM-3 + NK cells can kill K562 cells by releasing IFN-γ ( 158 – 160 ).…”

Section: Car-nk Cell and Immune Checkpoint Therapiesmentioning

confidence: 99%

Clinical application and prospect of immune checkpoint inhibitors for CAR-NK cell in tumor immunotherapy

Yang

Zhao²,

Sun³

et al. 2023

Front. Immunol.

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Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells is an attractive research field in tumor immunotherapy. While CAR is genetically engineered to express certain molecules, it retains the intrinsic ability to recognize tumor cells through its own receptors. Additionally, NK cells do not depend on T cell receptors for cytotoxic killing. CAR-NK cells exhibit some differences to CAR-T cells in terms of more precise killing, numerous cell sources, and increased effectiveness in solid tumors. However, some problems still exist with CAR-NK cell therapy, such as cytotoxicity, low transfection efficiency, and storage issues. Immune checkpoints inhibit immune cells from performing their normal killing function, and the clinical application of immune checkpoint inhibitors for cancer treatment has become a key therapeutic strategy. The application of CAR-T cells and immune checkpoint inhibitors is being evaluated in numerous ongoing basic research and clinical studies. Immune checkpoints may affect the function of CAR-NK cell therapy. In this review, we describe the combination of existing CAR-NK cell technology with immune checkpoint therapy and discuss the research of CAR-NK cell technology and future clinical treatments. We also summarize the progress of clinical trials of CAR-NK cells and immune checkpoint therapy.

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“… 40 , 68 Overall, the functional significance of TIM3 upregulation on several tumor-infiltrating T and innate cells, such as NK cells and dendritic cells (DCs), within tumors is still to be completely defined. 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 …”

Section: Introductionmentioning

confidence: 99%

Natural killer cells and immune-checkpoint inhibitor therapy: Current knowledge and new challenges

Poggi

Zocchi

2022

Molecular Therapy - Oncolytics

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The discovery of immune checkpoints (ICs) and the development of specific blockers to relieve immune effector cells from this inhibiting mechanism has changed the view of anti-cancer therapy. In addition to cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed death 1 (PD1), classical ICs of T lymphocytes and recently described also on a fraction of natural killer (NK) cells, several NK cell receptors, including killer immunoglobulin-like inhibitory receptors (KIRs) and NGK2A, have been recognized as checkpoint members typical of the NK cell population. This offers the opportunity of a dual-checkpoint inhibition approach, targeting classical and non-classical ICs and leading to a synergistic therapeutic effect. In this review, we will overview and discuss this new perspective, focusing on the most relevant candidates for this role among the variety of potential NK ICs. Beside listing and defining classical ICs expressed also by NK cells, or non-classical ICs either on T or on NK cells, we will address their role in NK cell survival, chronic stimulation or functional exhaustion, and the potential relevance of this phenomenon on anti-tumor immune response. Furthermore, NK ICs will be proposed as possible new targets for the development of efficient combined immunotherapy, not forgetting the relevant concerns that may be raised on NK IC blockade. Finally, the impact of epigenetic drugs in such a complex therapeutic picture will be briefly addressed.

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The inhibitory receptor Tim-3 fails to suppress IFN-γ production via the NFAT pathway in NK-cell, unlike that in CD4+ T cells

Cited by 9 publications

References 28 publications

Negative Regulation and Protective Function of Natural Killer Cells in HIV Infection: Two Sides of a Coin

Negative Regulation and Protective Function of Natural Killer Cells in HIV Infection: Two Sides of a Coin

Clinical application and prospect of immune checkpoint inhibitors for CAR-NK cell in tumor immunotherapy

Natural killer cells and immune-checkpoint inhibitor therapy: Current knowledge and new challenges

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