Activity of IL-12/15/18 primed natural killer cells against hepatocellular carcinoma

Zhuang, Lihui; Fulton, Rebecca; Rettman, Pauline; Sayan, Emre; Coad, Jonathan; Al‐Shamkhani, Aymen; Khakoo, Salim I.

doi:10.1007/s12072-018-9909-3

Cited by 40 publications

(28 citation statements)

References 28 publications

(24 reference statements)

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“…For example, IL-15 can strikingly augment the degranulation response to target cells of tumor-infiltrating NK cells to a higher percentage. 179,199 NK cell defects induced by alcohol consumption are extrinsic but not intrinsic, and recovery of IL-15 in the microenvironment is critical to restore NK cell function in alcoholics. 123 Systemic activation of innate immune cells, including NK cells, DCs, and macrophages, by the injection of poly I:C at the precancer stage was found to robustly suppress liver tumorigenesis induced by either the loss of PTEN or chemical carcinogens, as well as associated hepatosteatosis.…”

Section: Cytokines or Immune Stimulatorsmentioning

confidence: 99%

Innate lymphocytes: pathogenesis and therapeutic targets of liver diseases and cancer

Chen

Tian

2020

Cell Mol Immunol

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The liver is a lymphoid organ with unique immunological properties, particularly, its predominant innate immune system. The balance between immune tolerance and immune activity is critical to liver physiological functions and is responsible for the sensitivity of this organ to numerous diseases, including hepatotropic virus infection, alcoholic liver disease, nonalcoholic fatty liver disease, autoimmune liver disease, and liver cancer, which are major health problems globally. In the past decade, with the discovery of liver-resident natural killer cells, the importance of innate lymphocytes with tissue residency has gradually become the focus of research. In this review, we address the current knowledge regarding hepatic innate lymphocytes with unique characteristics, including NK cells, ILC1/2/3s, NKT cells, γδ T cells, and MAIT cells, and their potential roles in liver homeostasis maintenance and the progression of liver diseases and cancer. A better understanding of the immunopathogenesis of hepatic innate lymphocytes will be helpful for proposing effective treatments for liver diseases and cancer.

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Section: Cytokines or Immune Stimulatorsmentioning

confidence: 99%

Innate lymphocytes: pathogenesis and therapeutic targets of liver diseases and cancer

Chen

Tian

2020

Cell Mol Immunol

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“…IL-12/15/18-preactivated NK cells have emerged as a powerful tool to treat leukemia 11 , and their potential is also being explored in therapies against other malignancies [13][14][15]17 .…”

Section: Discussionmentioning

confidence: 99%

“…Current knowledge indicates that there are several differences between non-preactivated and CIML NK cells at phenotypic and functional levels 11,12,23,[25][26][27]48,49,[13][14][15][16][19][20][21][22] .…”

Section: Discussionmentioning

confidence: 99%

“…These cells have been proven to be useful in mouse and rat models of several malignancies, including acute myeloid leukemia, T-cell acute lymphoblastic leukemia, multiple myeloma, lymphoma, melanoma, ovarian cancer and hepatocellular carcinoma [11][12][13][14][15][16][17] . Regarding to humans, CIML NK cells have shown their safety and efficacy in the treatment of acute myeloid leukemia patients 11 , and are currently being tested in several clinical trials (NCT01898793, NCT02782546, NCT03068819, NCT04024761, NCT04290546 and NCT04354025, from clinicaltrials.gov).…”

Section: Introductionmentioning

confidence: 99%

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Human cytokine-induced memory-like NK cells preserve increased glycolysis but the glycolytic-dependence of their effector functions differ between stimuli

Terrén

Orrantia

Mosteiro

et al. 2020

Preprint

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Natural Killer (NK) cells acquire memory-like properties following a brief stimulation with IL-12, IL-15 and IL-18. These IL-12/15/18-stimulated NK cells, also known as cytokine-induced memory-like (CIML) NK cells, have been revealed as a powerful tool in cancer immunotherapy due to their persistence in the host and their increased effector functions. Several studies have shown that NK cells modulate their metabolism in response to cytokine-stimulation and other stimuli, suggesting that there is a link between metabolism and cellular functions. In this paper, we have analyzed metabolic changes associated to IL-12/15/18-stimulation and the relevance of glycolytic pathway for NK cell effector functions. We have found that CIML NK cells are able to retain increased glycolytic machinery seven days after cytokine withdrawal. Furthermore, we found that glycolytic inhibition with 2-DG is stimuli-dependent and that differently affects to distinct effector functions. These findings may have implications in the design of NK cell-based cancer immunotherapies.

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“…The activity and cytotoxicity function of NK cells is controlled by different cytokines such as IL-2, IL-12, IL-18, and IL-1, leading to upregulation of the expression of certain activating receptors [ 92 , 93 , 94 ]. Specifically, IL-2 cytokine has been utilized as an effective treatment for some malignancies and is currently used for immunotherapy.…”

Section: Role Of Innate Cells In Breast Cancermentioning

confidence: 99%

Understanding the Role of Innate Immune Cells and Identifying Genes in Breast Cancer Microenvironment

Shihab

Khalil

Elemam

et al. 2020

Cancers

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The innate immune system is the first line of defense against invading pathogens and has a major role in clearing transformed cells, besides its essential role in activating the adaptive immune system. Macrophages, dendritic cells, NK cells, and granulocytes are part of the innate immune system that accumulate in the tumor microenvironment such as breast cancer. These cells induce inflammation in situ by secreting cytokines and chemokines that promote tumor growth and progression, in addition to orchestrating the activities of other immune cells. In breast cancer microenvironment, innate immune cells are skewed towards immunosuppression that may lead to tumor evasion. However, the mechanisms by which immune cells could interact with breast cancer cells are complex and not fully understood. Therefore, the importance of the mammary tumor microenvironment in the development, growth, and progression of cancer is widely recognized. With the advances of using bioinformatics and analyzing data from gene banks, several genes involved in NK cells of breast cancer individuals have been identified. In this review, we discuss the activities of certain genes involved in the cross-talk among NK cells and breast cancer. Consequently, altering tumor immune microenvironment can make breast tumors more responsive to immunotherapy.

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Activity of IL-12/15/18 primed natural killer cells against hepatocellular carcinoma

Cited by 40 publications

References 28 publications

Innate lymphocytes: pathogenesis and therapeutic targets of liver diseases and cancer

Innate lymphocytes: pathogenesis and therapeutic targets of liver diseases and cancer

Human cytokine-induced memory-like NK cells preserve increased glycolysis but the glycolytic-dependence of their effector functions differ between stimuli

Understanding the Role of Innate Immune Cells and Identifying Genes in Breast Cancer Microenvironment

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