Antibody‐dependent cellular cytotoxicity toward neuroblastoma enhanced by activated invariant natural killer T cells

Mise, Naoko; Takami, Mariko; Suzuki, Akane; Kamata, Toshihide; Harada, Kazuaki; Hishiki, Tomoro; Saito, Takeshi; Terui, Keita; Mitsunaga, Tetsuya; Nakata, M.; Ikeuchi, Takayuki; Nakayama, Toshinori; Yoshida, Hideo; Motohashi, Shinichiro

doi:10.1111/cas.12882

Cited by 20 publications

(12 citation statements)

References 37 publications

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“…Additional blockade of PDL1 expressed on tumor cell lines resulted in enhanced direct cytotoxicity of the stimulated iNKT cells. Since iNKT cells are reported to not directly exhibit antibody-dependent cellular cytotoxicity (ADCC) [35], we concluded that PDL1 blockade enhances cytotoxic functions of iNKT cells. In addition, we found that anti-PDL1 antibody only improved Th1 cytokine production, whereas PDL2 blockade appeared to increase IL-4 secretion.…”

Section: Discussionmentioning

confidence: 98%

Blockade of programmed death-1/programmed death ligand pathway enhances the antitumor immunity of human invariant natural killer T cells

Kamata

Suzuki

Mise

et al. 2016

Cancer Immunol Immunother

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The role of invariant natural killer T (iNKT) cells in antitumor immunity has been studied extensively, and clinical trials in patients with advanced cancer have revealed a prolonged survival in some cases. In recent years, humanized blocking antibodies against co-stimulatory molecules such as PD-1 have been developed. The enhancement of T cell function is reported to improve antitumor immunity, leading to positive clinical effects. However, there are limited data on the role of PD-1/programmed death ligand (PDL) molecules in human iNKT cells. In this study, we investigated the interaction between PD-1 on iNKT cells and PDL on antigen-presenting cells (APCs) in the context of iNKT cell stimulation. The blockade of PDL1 at the time of stimulation resulted in increased release of helper T cell (Th) 1 cytokines from iNKT cells, leading to the activation of NK cells. The direct antitumor function of iNKT cells was also enhanced after stimulation with anti-PDL1 antibody-treated APCs. According to these results, we conclude that the co-administration of anti-PDL1 antibody and alpha-galactosylceramide (αGalCer)-pulsed APCs enhances iNKT cell-mediated antitumor immunity.Electronic supplementary materialThe online version of this article (doi:10.1007/s00262-016-1901-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 98%

Blockade of programmed death-1/programmed death ligand pathway enhances the antitumor immunity of human invariant natural killer T cells

Kamata

Suzuki

Mise

et al. 2016

Cancer Immunol Immunother

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“…Different from CD56+ T cells, we found iNKT expressed less CD16 than CD56+ T cells and failed to response to Ab-coated P815 cells, indicating that iNKT was unable to mediate ADCC responses though shared some NK characteristics. Another study has also found that iNKT cells did not mediated killing of neuroblastoma cell lines in the presence of a relevant antibody, although ADCC of mediated by NK cells was enhanced by activated iNKT cells [38]. CD56+ T cells were heterozygous cell population and could be subdivided into CD4+, CD8+, and DN subsets.…”

Section: Discussionmentioning

confidence: 99%

Antibody-dependent CD56+ T cell responses are functionally impaired in long-term HIV-1 infection

et al. 2016

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BackgroundAntibody-dependent cellular cytotoxicity (ADCC), which mainly mediated by natural killer (NK) cells, may play a critical role in slowing human immunodeficiency virus type-1 (HIV-1) disease progression and protecting from HIV-1 infection. Besides classic NK cells, CD56+ T cells also have some NK cell-like properties, such as the large granular lymphocyte morphology and the capacity to destroy NK-sensitive target cells. However, little is known about the potentials of antibody-dependent CD56+ T cell responses and the association between antibody-dependent CD56+ T cell responses and HIV-1 disease progression.ResultsIn the present study, we showed evidences that, in addition to NK cells, CD56+ T cells could generate degranulation upon CD16 cross-linking. Ex vivo study showed that FcγRIII (CD16)-mediated CD56+ T cell responses were distinctly induced by IgG antibody-bound P815 cells. Comparatively, CD56− T cells and invariant NKT (CD3+ 6B11+) failed to induce antibody-dependent activation. Antibody-dependent CD56+ T cell responses were mainly ascribed to CD4/CD8 double negative subset and were functionally impaired in long-term HIV-1-infected former plasma donors, regardless of hepatitis C virus (HCV) coinfection status. Also, CD56+ T cell-mediated HIV-1-specific antibody-dependent responses were declined in men who have sex with men with HIV-1 infection over 3 years. Finally, we showed that matrix metalloprotease (MMP) inhibitor GM6001 could partially restored antibody-dependent CD56+ T cell responses of chronic HIV-1-infected subjects.ConclusionsOur results suggested that CD56+ T cells could mediate ADCC responses and the responses were impaired in chronic HIV-1 infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-016-0313-6) contains supplementary material, which is available to authorized users.

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“…NLF cells also have low GD2 expression and high metastatic ability. 35 Moreover, NLF cells, like many high-risk NBs, may induce a tolerogenic immune environment due to their significant immunosuppressive activity, mainly based on inhibition of dendritic cell differentiation and activation. 36…”

Section: Introductionmentioning

confidence: 99%

<p>Nanomicellar Lenalidomide–Fenretinide Combination Suppresses Tumor Growth in an <em>MYCN</em> Amplified Neuroblastoma Tumor</p>

Orienti

Farruggia

Nguyen

et al. 2020

IJN

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In a previous study, we demonstrated that the combination of fenretinide with lenalidomide, administered by a novel nanomicellar formulation (FLM), provided a strong antitumor effect in a neuroblastoma TrkB-expressing tumor. In this study, we tested the nanomicellar combination in an MYCN amplified neuroblastoma xenograft to assess its efficacy in different tumor genotypes and evaluate the interactions of the nanomicelles with the tumor cells. Experimental Design: FLM was administered to mice bearing human NLF xenografts to evaluate its efficacy in comparison with the nanomicelles containing fenretinide alone (FM). Confocal laser-scanning fluorescence microscopy images of the NLF cells treated with FLM and FM allowed us to estimate the nanomicelle ability to transport the encapsulated drugs inside the tumor cells. Flow cytometric analysis of the cells from treated tumors was performed to assess the effect of treatment on GD2 expression and NK cell infiltration. Results: FLM and FM decreased the growth of NLF xenografts at comparable extents during the treatment period. Afterwards, FLM induced a progressive tumor regression without regrowth, while FM treatment was followed by regrowth within 15-20 days after the end of treatment. Both FLM and FM were able to penetrate the tumor cells transporting the encapsulated drugs. FLM transported higher amount of fenretinide inside the cells. Also, FLM treatment strongly increased GD2 expression in treated tumors and slightly decreased the NK infiltration compared to FM. Conclusion: FLM treatment induced a superior antitumor response than FM in NLF xenografts, presumably due to the combined effects of fenretinide cytotoxicity and lenalidomide antiangiogenic activity. The ability of FLM to penetrate tumor cells, transporting the encapsulated drugs, substantially improved the therapeutic efficiency of this system. Moreover, the enhancement of GD2 expression in FLM treated tumors offers the possibility to further increase the antitumor effect by the use of anti-GD2 CART cells and anti-GD2 antibodies in combination with FLM in multimodal therapies.

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Antibody‐dependent cellular cytotoxicity toward neuroblastoma enhanced by activated invariant natural killer T cells

Cited by 20 publications

References 37 publications

Blockade of programmed death-1/programmed death ligand pathway enhances the antitumor immunity of human invariant natural killer T cells

Blockade of programmed death-1/programmed death ligand pathway enhances the antitumor immunity of human invariant natural killer T cells

Antibody-dependent CD56+ T cell responses are functionally impaired in long-term HIV-1 infection

<p>Nanomicellar Lenalidomide–Fenretinide Combination Suppresses Tumor Growth in an <em>MYCN</em> Amplified Neuroblastoma Tumor</p>

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