NK cell-based cancer immunotherapy: from basic biology to clinical application

Li, Yang; Yin, Jie; Li, Ting; Huang, Shan; Han, Yanping; Leavenworth, Jianmei W.; Wang, Xi

doi:10.1007/s11427-015-4970-9

Cited by 50 publications

(43 citation statements)

References 125 publications

(136 reference statements)

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“…From the foregoing, decidual immune cells form a unique microenvironment, have a dynamic development process in pregnancy, peak in the recasting spiral artery phase, and even reach 30%-40% of all local cells in early pregnancy decidual + phenotype and are endowed with ADCC function (Ni et al, 2013;Li et al, 2015;Wang et al, 2015). pbNK cells also express CD11a and CD11b, forming LFA-1 and MAC-1, respectively, with CD18, which all have ICAM-1 as their corresponding ligand.…”

Section: T Cellsmentioning

confidence: 99%

Decidual natural killer cells and the immune microenvironment at the maternal-fetal interface

Wei

2016

Sci. China Life Sci.

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During early pregnancy, an orchestrated evolutionary maternal adaption toward tolerance of the semiallogeneic fetus is required to ensure decidualization and early embryo development. Remodeling of the immune system involves natural killer cells (NKs), macrophages, T cells and dendritic cells (DCs) altering the microenvironment in the deciduas. In particular, a unique population of NK cells with a CD56 bright CD16− phenotype in the decidua has been proposed to play a key role in the maternal adaptation to pregnancy. However, there is a tendency for pregnancy immunology to reflect transplantation immunology regarding the assumption that the maternal immune system should be suppressed. This tendency is misleading. We discuss how the immune system is formed in early deciduas and the interactions between maternal NK cells and fetal growth. We propose that the maternal immune response must not be fully suppressed and is even necessary for the local response of uterine NK cells. NK cells, decidua, fetal growth, the immune microenvironment Citation:Fu, B., and Wei, H. (2016). Decidual natural killer cells and the immune microenvironment at the maternal-fetal interface.

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Section: T Cellsmentioning

confidence: 99%

Decidual natural killer cells and the immune microenvironment at the maternal-fetal interface

Wei

2016

Sci. China Life Sci.

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“…Covalent modification of histones by chromatin-modifying enzymes can fundamentally alter the organization and function of chromatin, and serves as a crucial regulator of cell fate determination, playing an essential role in many biological processes, including immune regulation [13–16]. According to our recent data, inhibition of histone methyltransferase Ezh2 enzymatic activity through small molecule inhibitors could enhance NK cell lineage commitment and promote the survival of both NKp and its progeny.…”

Section: Discussionmentioning

confidence: 99%

Chromatin state dynamics during NK cell activation

Wang

Yin

et al. 2017

Oncotarget

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Studies of Natural Killer (NK) cell cytotoxicity have mainly focused on the balance of activating and inhibitory receptors, signaling transduction, calcium influx, formation of immune synapse, and cytolytic degranulation. However, little is known about the chromatin state of NK cells and the impact of its changes during target recognition. In this study, we investigate the contribution of chromatin state dynamics during NK cell activation by comprehensively analyzing a set of microarray data and two sets of Chromatin Immunoprecipitation-Sequencing (ChIP-seq) data. We find that the expression of several histone demethylases and methyltransferases was influenced upon stimulation. Furthermore, we notice that a series of genes, including PI3KCA, NFATC1and TNFSF9, which play important roles during NK cell activation, were at ‘poised’ state prior to activation, and that modifications of H3K4me3 and H3K27me3 on these promotors were sensitive to stimulation with Phorbol Myristate Acetate (PMA) and Ionomycin (Iono) in the NK92MI cell line. Finally, we demonstrate that a series of small molecule inhibitors, which are specific to H3K4 and H3K27 modification, enhance degranulation or the expression levels of IFN-γ and TNF-α. Our results suggest that the histone modification state has a profound impact on NK cell activation, and provide novel insights into the regulation of NK cellular cytotoxicity and immunoregulatory function by chromatin state dynamics.

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“…Upon activation NK cells directly kill infected cells through cytotoxicity or boost immune responses via cytokine secretion. NK cells may exert either positive or negative effects on oHSV therapy, depending on several factors such as virus type, dose, and replication rate (36, 37). An optimal balance of NK activating and inhibiting signals may be particularly relevant for oHSV-based therapies.…”

Section: Innate Immunity In Ohsv Therapymentioning

confidence: 99%

Modulation of the Intratumoral Immune Landscape by Oncolytic Herpes Simplex Virus Virotherapy

2017

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Vaccines and immunotherapeutic approaches to cancers with the advent of immune checkpoint inhibitors and chimeric antigen receptor-modified T cells have recently demonstrated preclinical success and entered clinical trials. Despite advances in these approaches and combinatorial therapeutic regimens, depending on the nature of the cancer and the immune and metabolic landscape within the tumor microenvironment, current immunotherapeutic modalities remain inadequate. Recent clinical trials have demonstrated clear evidence of significant, and sometimes dramatic, antitumor activity, and long-term survival effects of a variety of oncolytic viruses (OVs), particularly oncolytic herpes simplex virus (oHSV). Acting as a multifaceted gene therapy vector and potential adjuvant-like regimens, oHSV can carry genes encoding immunostimulatory molecules in its genome. The oncolytic effect of oHSV and the inflammatory response that the virus stimulates provide a one-two punch at attacking tumors. However, mechanisms underlying oHSV-induced restoration of intratumoral immunosuppression demand extensive research in order to further improve its therapeutic efficacy. In this review, we discuss the current OV-based therapy, with a focus on the unique aspects of oHSV-initiated antiviral and antitumor immune responses, arising from virus-mediated immunological cell death to intratumoral innate and adaptive immunity.

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NK cell-based cancer immunotherapy: from basic biology to clinical application

Cited by 50 publications

References 125 publications

Decidual natural killer cells and the immune microenvironment at the maternal-fetal interface

Decidual natural killer cells and the immune microenvironment at the maternal-fetal interface

Chromatin state dynamics during NK cell activation

Modulation of the Intratumoral Immune Landscape by Oncolytic Herpes Simplex Virus Virotherapy

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