Terminal differentiation of bone marrow NK cells and increased circulation of TIGIT<sup>+</sup> NK cells may be related to poor outcome in acute myeloid leukemia

Zeng, Xiangbo; Yao, Danlin; Zhang, Yikai; Lai, Jing; Zhong, Jun; Zha, Xianfeng; Lu, Yuhong; Jin, Zhenyi; Chen, Shaohua; Li, Yangqiu; Xu, Ling

doi:10.1111/ajco.13723

Cited by 7 publications

(5 citation statements)

References 39 publications

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“…The expression of TIGIT is also typically upregulated and indicates poor clinical outcomes in several hematologic malignancies. First, in patients with chronic lymphocytic leukemia (CLL), AML, or adult acute lymphoblastic leukemia (ALL), TIGIT is commonly upregulated on CD4 + T cells, CD8 + T cells, Foxp3 + γδ T cells, or NK cells compared with healthy individuals [64][65][66][67][68][69][70]. Notably, TIGIT leads to CLL anergy by downregulating B cell receptor signaling [71].…”

Section: Tigit In Solid Tumors and Hematological Malignanciesmentioning

confidence: 99%

Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials

et al. 2023

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Over the past decade, immune checkpoint inhibitors (ICIs) have emerged as a revolutionary cancer treatment modality, offering long-lasting responses and survival benefits for a substantial number of cancer patients. However, the response rates to ICIs vary significantly among individuals and cancer types, with a notable proportion of patients exhibiting resistance or showing no response. Therefore, dual ICI combination therapy has been proposed as a potential strategy to address these challenges. One of the targets is TIGIT, an inhibitory receptor associated with T-cell exhaustion. TIGIT has diverse immunosuppressive effects on the cancer immunity cycle, including the inhibition of natural killer cell effector function, suppression of dendritic cell maturation, promotion of macrophage polarization to the M2 phenotype, and differentiation of T cells to regulatory T cells. Furthermore, TIGIT is linked with PD-1 expression, and it can synergize with PD-1/PD-L1 blockade to enhance tumor rejection. Preclinical studies have demonstrated the potential benefits of co-inhibition of TIGIT and PD-1/PD-L1 in enhancing anti-tumor immunity and improving treatment outcomes in several cancer types. Several clinical trials are underway to evaluate the safety and efficacy of TIGIT and PD-1/PD-L1 co-inhibition in various cancer types, and the results are awaited. This review provides an overview of the mechanisms of TIGIT and PD-1/PD-L1 co-inhibition in anti-tumor treatment, summarizes the latest clinical trials investigating this combination therapy, and discusses its prospects. Overall, co-inhibition of TIGIT and PD-1/PD-L1 represents a promising therapeutic approach for cancer treatment that has the potential to improve the outcomes of cancer patients treated with ICIs.

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Section: Tigit In Solid Tumors and Hematological Malignanciesmentioning

confidence: 99%

Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials

et al. 2023

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“…In addition, while the frequency of killer cell lectin-like receptor G1 (KLRG1)- and TIGIT-expressing NK cells was increased in peripheral blood of novo patients, it was recovered in patients after chemotherapy. Moreover, the frequency of terminally differentiated NK cells (CD56 dim CD16 + CD57 + ), which had a potent cytotoxic function and low replication capacity, was increased in the bone marrow of novo AML patients and correlated with a lower survival rate [ 67 ]. Tang et al .…”

Section: Exhausted Nk Cells and Leukemiamentioning

confidence: 99%

The role of exhausted natural killer cells in the immunopathogenesis and treatment of leukemia

Barshidi,

Ardeshiri,

Ebrahimi

et al. 2024

Cell Commun Signal

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The immune responses to cancer cells involve both innate and acquired immune cells. In the meantime, the most attention has been drawn to the adaptive immune cells, especially T cells, while, it is now well known that the innate immune cells, especially natural killer (NK) cells, play a vital role in defending against malignancies. While the immune cells are trying to eliminate malignant cells, cancer cells try to prevent the function of these cells and suppress immune responses. The suppression of NK cells in various cancers can lead to the induction of an exhausted phenotype in NK cells, which will impair their function. Recent studies have shown that the occurrence of this phenotype in various types of leukemic malignancies can affect the prognosis of the disease, and targeting these cells may be considered a new immunotherapy method in the treatment of leukemia. Therefore, a detailed study of exhausted NK cells in leukemic diseases can help both to understand the mechanisms of leukemia progression and to design new treatment methods by creating a deeper understanding of these cells. Here, we will comprehensively review the immunobiology of exhausted NK cells and their role in various leukemic malignancies.

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“… [ 121 ] AML Human Newly diagnosed patient PB and bone marrow NK HC High KLRG1 can block the anti-leukemia function of NK cells. [ 118 ] MM Human Newly diagnosed patient PB and bone marrow Cytotoxic T HC High The function of KLRG1-positive cytotoxic T cells is impaired. [ 120 ] Mouse C57BL/KaLwRij (MM) Bone marrow NK C57BL/KaLwRij (WT) Low Decreased KLRG1 − NK cells, KLRG1-negative NK cells have decreased and impaired transit to the bone marrow that helps tumors evade NK cell-mediated immune surveillance.…”

Section: Regulation Of Immune Signaling By Klrg1mentioning

confidence: 99%

“…HMs are a group of hematopoietic diseases characterized by a high degree of malignancy, complex treatment, and poor prognosis. KLRG1 expression is increased on a variety of immune cells in patients with a variety of HMs, including chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), acute myeloid leukemia (AML), and multiple myeloma (MM) [117][118][119]. KLRG1-positive cells have impaired proliferation ability and can bind to ligands to inhibit CD8 + T-cell effector function, leading to immune dysfunction in patients [117][118][119][120][121].…”

Section: Klrg1 In Hematological Malignanciesmentioning

confidence: 99%

“…KLRG1 expression is increased on a variety of immune cells in patients with a variety of HMs, including chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), acute myeloid leukemia (AML), and multiple myeloma (MM) [117][118][119]. KLRG1-positive cells have impaired proliferation ability and can bind to ligands to inhibit CD8 + T-cell effector function, leading to immune dysfunction in patients [117][118][119][120][121]. In CLL patients, the expression levels of KLRG1 + CD8 + T-cells and plasma sE-cad are increased.…”

Section: Klrg1 In Hematological Malignanciesmentioning

confidence: 99%

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The role of KLRG1: a novel biomarker and new therapeutic target

Zhang,

Chen,

Tang

et al. 2024

Cell Commun Signal

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Killer cell lectin-like receptor G1 (KLRG1) is an immune checkpoint receptor expressed predominantly in NK and T-cell subsets that downregulates the activation and proliferation of immune cells and participates in cell-mediated immune responses. Accumulating evidence has demonstrated the importance of KLRG1 as a noteworthy disease marker and therapeutic target that can influence disease onset, progression, and prognosis. Blocking KLRG1 has been shown to effectively mitigate the effects of downregulation in various mouse tumor models, including solid tumors and hematologic malignancies. However, KLRG1 inhibitors have not yet been approved for human use, and the understanding of KLRG1 expression and its mechanism of action in various diseases remains incomplete. In this review, we explore alterations in the distribution, structure, and signaling pathways of KLRG1 in immune cells and summarize its expression patterns and roles in the development and progression of autoimmune diseases, infectious diseases, and cancers. Additionally, we discuss the potential applications of KLRG1 as a tool for tumor immunotherapy.

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Terminal differentiation of bone marrow NK cells and increased circulation of TIGIT⁺ NK cells may be related to poor outcome in acute myeloid leukemia

Cited by 7 publications

References 39 publications

Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials

Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials

The role of exhausted natural killer cells in the immunopathogenesis and treatment of leukemia

The role of KLRG1: a novel biomarker and new therapeutic target

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Terminal differentiation of bone marrow NK cells and increased circulation of TIGIT+ NK cells may be related to poor outcome in acute myeloid leukemia

Cited by 7 publications

References 39 publications

Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials

Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials

The role of exhausted natural killer cells in the immunopathogenesis and treatment of leukemia

The role of KLRG1: a novel biomarker and new therapeutic target

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Product

Resources

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Terminal differentiation of bone marrow NK cells and increased circulation of TIGIT⁺ NK cells may be related to poor outcome in acute myeloid leukemia