Influence of In Vitro IL-2 or IL-15 Alone or in Combination with Hsp-70-Derived 14-mer Peptide (TKD) on the Expression of NK Cell Activatory and Inhibitory Receptors

Hromadníková, Ilona; Pirkova, Petra; Sedláčková, Lucie

doi:10.1155/2013/405295

Cited by 26 publications

(32 citation statements)

References 74 publications

(78 reference statements)

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“…Moreover, IL-2 activates CD56 dim NK cells, augmenting the production of perforin 15 and granzymes 15,34 , enhancing ADCC and antibody-independent (natural) cytotoxicity as well as IFN-γ production 15,35–43 . Activating receptors on this subset are also up-regulated by IL-2, including NCRs 44–46 , NKG2D 15,33,44 , and DNAM-1 44–46 .…”

Section: Enhancing Nk Cell Function With Cytokines Drugs and Toll-limentioning

confidence: 99%

NK Cell-based Immunotherapies in Pediatric Oncology

McDowell

Hank

DeSantes

et al. 2015

Journal of Pediatric Hematology/Oncology

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The past decade has seen several anti-cancer immunotherapeutic strategies transition from “promising preclinical models” to treatments with proven clinical activity or benefit. In 2013, the journal Science selected the field of Cancer Immunotherapy as the overall number-1 breakthrough for the year in all of scientific research. In the setting of cancer immunotherapy for adult malignancies, many of these immunotherapy strategies have relied on the cancer patient’s endogenous anti-tumor T cell response. While much promising research in pediatric oncology is similarly focused on T cell reactivity, several pediatric malignancies themselves, or the chemo-radiotherapy used to achieve initial responses, can be associated with profound immune suppression, particularly of the T cell system. A separate component of the immune system, also able to mediate anti-tumor effects and less suppressed by conventional cancer treatment, is the NK cell system. In recent years, several distinct immunotherapeutic approaches that rely on the activity of NK cells have moved from preclinical development into clinical testing, and some have shown clear antitumor benefit. This review provides an overview of NK cell-based immunotherapy efforts that are directed towards childhood malignancies, with an emphasis on protocols that are already in clinical testing.

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Section: Enhancing Nk Cell Function With Cytokines Drugs and Toll-limentioning

confidence: 99%

NK Cell-based Immunotherapies in Pediatric Oncology

McDowell

Hank

DeSantes

et al. 2015

Journal of Pediatric Hematology/Oncology

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“…NKG2D and TNF-a up-regulation was due to elevated pSTAT5 IL-2 was reported to promote the expression of NKG2D [40,41] and TNF-a [42,43] and was the only cytokine added in the duration of cell expansion and rapamycin treatment. Besides, STAT5 activation was also reported to promote TNF-a [44,45] and NKG2D (see Supplemental data in ref.…”

Section: The Blocking Of Nkg2d and Tnf-a Suppressed Cytotoxicity Of Rmentioning

confidence: 99%

mTOR inhibition potentiates cytotoxicity of Vγ4 γδ T cells via up-regulating NKG2D and TNF-α

Cao

Wang

et al. 2016

Journal of Leukocyte Biology

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γδ T cells play a critical role in early anti-tumor immunity and perform cytotoxicity via NKG2D for recognition and multiple cytotoxic factors for tumor killing. Recent studies have demonstrated pivotal roles of mTOR-mediated metabolism in the maturation, differentiation, and effector function of diverse immune cells, including DCs, NK cells, CD4 T cell subsets, and CD8 T cells, but the role of mTOR signaling in γδ T cells is barely known. Here, we showed that suppressing mTOR signaling in in vitro-expanded Vγ4 γδ T cells via the mechanistic inhibitor rapamycin enhanced their cytotoxicity against multiple tumor cell lines, and these cells performed better tumor-suppressing effects upon adoptive therapy. Further investigation revealed that elevated cytotoxicity was a result of up-regulation of NKG2D and TNF-α. Moreover, rapamycin treatment significantly decreased the expression of CISH and increased pSTAT5. The inhibition of STAT5 pathways via siRNA interference or a specific inhibitor eliminated the up-regulation of NKG2D and TNF-α in rapamycin-treated Vγ4 γδ T cells. These results uncovered an important role of mTOR signaling in the cytotoxic effector function of γδ T cells and provided a potential strategy to improve γδ T cell-based cancer immunotherapy.

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“…Expression of DNAM‐1 on NK cells can also be regulated by soluble factors and cell–cell interactions . In humans, IL‐2 or IL‐15 alone or in combination with heat‐shock protein 70‐derived 14‐mer peptide, granulocyte–macrophage colony‐stimulating factor/IL‐2 fusion protein, and glucocorticoid up‐regulates DNAM‐1 expression, whereas indoleamine 2,3‐dioxygenase, transforming growth factor‐ β and chronic CD155 exposure by some tumour cells can down‐regulate DNAM‐1 expression on NK cells …”

Section: Expression and Modulation Of Dnam‐1 On Nk Cellsmentioning

confidence: 99%

Critical roles of co‐activation receptor DNAX accessory molecule‐1 in natural killer cell immunity

2015

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SummaryNatural killer (NK) cells, which can exert early and powerful anti-tumour and anti-viral responses, are important components of the innate immune system. DNAX accessory molecule-1 (DNAM-1) is an activating receptor molecule expressed on the surface of NK cells. Recent findings suggest that DNAM-1 is a critical regulator of NK cell biology. DNAM-1 is involved in NK cell education and differentiation, and also plays a pivotal role in the development of cancer, viral infections and immune-related diseases. However, tumours and viruses have developed multiple mechanisms to evade the immune system. They are able to impair DNAM-1 activity by targeting the DNAM-1 receptor-ligand system. We have reviewed the roles of DNAM-1, and its biological functions, with respect to NK cell biology and DNAM-1 chimeric antigen receptor-based immunotherapy.

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Influence of In Vitro IL-2 or IL-15 Alone or in Combination with Hsp-70-Derived 14-mer Peptide (TKD) on the Expression of NK Cell Activatory and Inhibitory Receptors

Cited by 26 publications

References 74 publications

NK Cell-based Immunotherapies in Pediatric Oncology

NK Cell-based Immunotherapies in Pediatric Oncology

mTOR inhibition potentiates cytotoxicity of Vγ4 γδ T cells via up-regulating NKG2D and TNF-α

Critical roles of co‐activation receptor DNAX accessory molecule‐1 in natural killer cell immunity

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