Assessment of the change in cetuximab‐induced antibody‐dependent cellular cytotoxicity activity of natural killer cells by steroid

Kumai, Takumi; Oikawa, Kensuke; Aoki, Naoko; Kimura, Shoji; Harabuchi, Yasuaki; Kobayashi, Hiroya

doi:10.1002/hed.23906

Cited by 13 publications

(14 citation statements)

References 22 publications

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“…Previously, GCs were demonstrated to prevent IL-15-mediated suppression of NK cells (Moustaki et al 2011 ). Also, GCs were shown to have moderate stimulatory effects on the expression of NKG2D and NKp30 in most treated patients (Kumai et al 2016 ). In addition, our results indicate that Dex increases the percentage of CD11b − CD27 + but decreases the percentage of CD11b + CD27 + NK cells.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, GCs were shown to suppress activities of NK cells (Kiecolt-Glaser et al 1987 ). In contrast, other studies did not observe any significant effect on survival of NK cells by dexamethasone (Dex) treatment (Kumai et al 2016 ). Moreover, GCs were recently shown to epigenetically suppress NK cell lytic activity (Eddy et al 2014 ).…”

Section: Introductionmentioning

confidence: 88%

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Regulatory effects of dexamethasone on NK and T cell immunity

2017

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Glucocorticoids (GCs) act via the intracellular glucocorticoid receptor (GR), which can regulate the expression of target genes. With regard to the immune system, GCs may affect both innate and adaptive immunity. Our study analyzed the immunoregulatory effects of dexamethasone (Dex) treatment on splenic T, Treg, NK and NKT cells by treating C57Bl6 mice with various doses of Dex. We observed that treatment with Dex decreased the number of NK cells in the spleen and suppressed their activity. In particular, the expression of both Ly49G and NKG2D receptors was decreased by Dex. However, Dex did not affect the population of NKT cells. With regard to splenic T cells, our results show a dose-dependent reduction in CD3+, CD4+, CD8+, CD44+ and CD8+CD122+ T cells, but a stimulatory effect on CD4+CD25+ regulatory T cells by Dex treatment. In addition, treatment with Dex suppressed anti-tumor immune response in a mouse EG7 tumor model. We conclude that Dex may suppress both T- and NK-mediated immunity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 88%

Regulatory effects of dexamethasone on NK and T cell immunity

2017

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“…These antibodies such as cetuximab and rituximab are capable of inducing antibody-dependent cellular cytotoxicity, antibody-dependent complement-mediated cytotoxicity, and antibody-dependent cellular phagocytosis and have shown promising clinical results in both solid and hematological tumor [68,69]. C-C chemokine receptor 4 (CCR4) is expressed on NKTL and might be a suitable target for the antibody therapy.…”

Section: Antibody Therapiesmentioning

confidence: 99%

Novel Targets for Natural Killer/T-cell Lymphoma Immunotherapy

2015

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SummaryExtranodal natural killer/T-cell lymphoma, nasal type (NKTL) is a rare but highly aggressive Epstein-Barr virus-related malignancy, which mainly occurs in nasopharygeal and nasal/paranasal areas. In addition to its high prevalence in Asian, Central American and South American populations, its incidence rate has been gradually increasing in Western countries. The current mainstay of treatment is a combination of multiple chemotherapies and irradiation. Although chemoradiotherapy can cure NKTL, it often causes severe and fatal adverse events. Because a growing body of evidence suggests that immunotherapy is effective against hematological malignancies, this treatment could provide an alternative to chemoradiotherapy for treatment of NKTL. In this review, we focus on how recent findings could be used to develop efficient immunotherapies against NKTL.

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“…4 Glucocorticoids and immunophilin ligands which are used to suppress the infusion reaction of mAb-based therapy could be options to avoid undesired ADCC. [5][6][7] However, these drugs inactivate various kinds of immune cells as well as NK cells, leading to susceptibility to pathogenic infection and reduced anti-cancer effects. 7 Thus, specific inhibitors of ADCC for non-target cells which express target antigens are preferable for this application.…”

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confidence: 99%

A peptide inhibitor of antibody-dependent cell-mediated cytotoxicity against EGFR/folate receptor-α double positive cells

et al. 2018

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Antibody-dependent cell-mediated cytotoxicity (ADCC) is caused by natural killer (NK) cells upon recognition of antigen-bound IgG FcγRIIIa. This mechanism is crucial for cytolysis of pathogen-infected cells and monoclonal antibody (mAb)-mediated elimination of cancer cells. However, there is concern that mAb-based cancer therapy induces ADCC against non-target cells expressing antigens. To date, no strategy has been reported to enhance the selectivity of ADCC to protect non-target cells expressing antigens. Here, we introduce a model inhibitor which specifically blocks ADCC of anti-EGFR mAbs towards EGFR/folate receptor α (FRα) double positive cells. This inhibitor recruits mAbs on the FRα of the cell surface independent of Fab antigen recognition. The resulting ternary and/or quaternary complexes formed on the cell surface suppress signal transduction of FcγRIIIa in NK cells, consequently leading to more specific ADCC.

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Assessment of the change in cetuximab‐induced antibody‐dependent cellular cytotoxicity activity of natural killer cells by steroid

Abstract: This is the first report that shows the negative affect of steroids in cancer treatment using therapeutic antibody. Attention needs to be paid for using steroids in tumor treatment.

Cited by 13 publications

References 22 publications

Regulatory effects of dexamethasone on NK and T cell immunity

Regulatory effects of dexamethasone on NK and T cell immunity

Novel Targets for Natural Killer/T-cell Lymphoma Immunotherapy

A peptide inhibitor of antibody-dependent cell-mediated cytotoxicity against EGFR/folate receptor-α double positive cells

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