Impaired Proliferative Response of Vα24 NKT Cells from Cancer Patients Against α-Galactosylceramide

Yanagisawa, Kazuhiko; Seino, Ken‐ichiro; Ishikawa, Yuriko; Nozue, Mutsumi; Todoroki, Takeshi; Fukao, Katashi

doi:10.4049/jimmunol.168.12.6494

Cited by 121 publications

(114 citation statements)

References 25 publications

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“…We have confirmed with considerably larger subject numbers in this study that the percentage of Va24 þ NKT cells in cancer patients does not significantly differ to that in healthy donors when all cancer types are considered collectively (Yanagisawa et al, 2002). Our data also support previous reports that NKT cell numbers are significantly reduced in patients with melanoma (Kawano et al, 1999a); however, in contrast to Motohashi et al (2002) decreased frequency and absolute number of NKT cells was not seen in lung cancer patients.…”

Section: Discussionsupporting

confidence: 92%

“…Significant reductions in PB NKT cell numbers have been reported in patients with melanoma, prostate cancer and lung cancer (Kawano et al, 1999a;Tahir et al, 2001;Motohashi et al, 2002), however in other studies the numbers of NKT cells in advanced cancer patients are comparable to those in healthy individuals (Yanagisawa et al, 2002). Variations in NKT cell function have also been described.…”

mentioning

confidence: 97%

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Modulation of human Vα24+Vβ11+ NKT cells by age, malignancy and conventional anticancer therapies

Crough

Purdie²,

Okai³

et al. 2004

Br J Cancer

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Immunotherapy strategies aimed at increasing human Va24 þ Vb11 þ natural killer T (NKT) cell numbers are currently a major focus. To provide further information towards the goal of NKT cell-based immunotherapy, we assessed the effects of age, cancer status and prior anticancer treatment on NKT cell numbers and their expansion capacity following a-galactosylceramide (a-GalCer) stimulation. The percentage and absolute number of peripheral blood NKT cells was assessed in 40 healthy donors and 109 solid cancer patientsResponsiveness to a-GalCer stimulation was also assessed in 28 of the cancer patients and 37 of the healthy donors. Natural killer T cell numbers were significantly reduced in melanoma and breast cancer patients. While NKT numbers decreased with age in healthy donors, NKT cells were decreased in these cancer subgroups despite age and sex adjustments. Prior radiation treatment was shown to contribute to the observed reduction in melanoma patients. Although cancer patient NKT cells were significantly less responsive to a-GalCer stimulation, they remained capable of substantial expansion. Natural killer T cells are therefore modulated by age, malignancy and prior anticancer treatment; however, cancer patient NKT cells remain capable of responding to a-GalCer-based immenotherapies.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 97%

Modulation of human Vα24+Vβ11+ NKT cells by age, malignancy and conventional anticancer therapies

Crough

Purdie²,

Okai³

et al. 2004

Br J Cancer

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“…13,[41][42][43][44] We reported that the number of Va24 1 NKT cells among PBMCs is reduced in patients with lung cancer but their ability to produce IFN-c remains intact. 13 In patients with advanced gastrointestinal cancers, the in vitro expansion of Va24 1 NKT cells was impaired, although it recovered partially by coculture with G-CSF.…”

Section: Discussionmentioning

confidence: 99%

Dendritic cell maturation by CD11c⁻ T cells and Vα24⁺ natural killer T‐cell activation by α‐Galactosylceramide

Ishikawa¹,

Motohashi²,

Ishikawa³

et al. 2005

Intl Journal of Cancer

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Human invariant Vα24+ natural killer T (NKT) cells display potent antitumor activity upon stimulation. Activation of endogenous Vα24+ NKT cells would be one strategy for the treatment of cancer patients. For example, dendritic cells (DCs) loaded with a glycolipid NKT cell ligand, α‐galactosylceramide (αGalCer, KRN7000), are a possible tool for the activation and expansion of functional Vα24+ NKT cells in vivo. In this report, we demonstrate that the levels of expansion and the ability to produce IFN‐γ of Vα24+ NKT cells induced by αGalCer‐loaded whole PBMCs cultured with IL‐2 and GM‐CSF (IL‐2/GM‐CSF‐cultured PBMCs) were superior to those of cells induced by monocyte‐derived CD11c+ DCs (moDCs) developed with IL‐4 and GM‐CSF. Interestingly, CD11c+ cells in the IL‐2/GM‐CSF‐cultured PBMCs showed a mature phenotype without further stimulation and exerted potent stimulatory activity on Vα24+ NKT cells to enable them to produce IFN‐γ preferentially at an extent equivalent to mature moDCs induced by stimulation with LPS or a cytokine cocktail. Cocultivation with CD11c− cells in the IL‐2/GM‐CSF‐cultured PBMCs induced maturation of moDCs. In particular, CD11c−CD3+ T cells appeared to play important roles in DC maturation. In addition, TNF‐α was preferentially produced by CD11c−CD3+ T cells in IL‐2/GM‐CSF‐cultured PBMCs and was involved in the maturation of moDCs. Thus, the maturation of DCs induced by CD11c− T cells through TNF‐α production appears to result in the efficient expansion and activation of Vα24+ NKT cells to produce IFN‐γ preferentially. © 2005 Wiley‐Liss, Inc.

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“…For example, NKT cells are reduced in advanced prostate cancer patients and have decreased proliferation and cytokine production compared with healthy controls. 36 Subsequent reports showed decreased proliferative invariant NKT cell responses from patients with a variety of neoplastic diseases 102 and showed that freshly isolated invariant NKT from patients with specifically progressive multiple myeloma had a marked decrease in IFN-␥ production. 103 Livers from patients with metastatic disesase show a reduced frequency of V␣24ϩ NKT cells compared with healthy controls.…”

Section: Role In Tumor Surveillancementioning

confidence: 99%

To be or not to be NKT: Natural killer T cells in the liver

2004

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N KT cells are a diverse group of cells that share features of both classical T cells and natural killer (NK) cells, and have similarly diverse functions. One of the complexities in understanding NKT cells involves sorting through the various terminology that has been applied to them in the emerging literature. 1,2 Functionally, a major subset of these cells are defined by reactivity against CD1d, which is one of five known glycolipid-binding nonpolymorphic major histocompatibility complex class 1-like glycoproteins: CD1a through e. 3 These glycoproteins appear to have evolved to facilitate recognition of nonprotein antigens-specifically glycolipid antigens, including those present in the cell walls of mycobacterial species. CD1d is constitutively expressed on a number of hematopoietic-derived antigenpresenting cell (APC) types-including B cells and myeloid cells-and can be expressed by human T cells as well as healthy hepatocytes. Physiological ligands for CD1d remain poorly defined, although both glycolipids and hydrophobic peptides bind to CD1 family molecules. 4,5 Most antigen studies have used the synthetic glycolipid ␣-galactosylceramide (␣GalCer), which binds to CD1d and activates a specific subset of both murine and human NKT cells in vitro and in vivo. 5,6 CD1d is remarkably conserved across mammalian species, with mouse and human CD1d having greater than 90% sequence homology. 7 Consequently, murine CD1d-reactive T cells recognize human CD1d, and vice versa. 8 After activation, NKT cells are highly versatile and can produce large amounts of interferon gamma (IFN-␥) and interleukin (IL)-4 9,10 as prototypic type 1 and type 2 cytokines, respectively, as well as display NK/lymphokine-activated killing-like FasL-mediated or perforin-dependent CD1d-specific cytotoxicity 11-14 thus potentially contributing to protective and pathogenic responses against multiple infectious agents and tumors.CD1d is expressed by dendritic cells (DCs), and ␣Gal-Cer-loaded DCs mediate activation of invariant NKT cells. [15][16][17][18] Although peripheral NKT cells can recognize and respond to other CD1d ϩ cells, their in vivo activation may be initiated by interactions with DCs and possibly B cells. The interactions between invariant NKT cells and DCs share many features of interactions between conventional CD4 ϩ T cells and DCs. DCs pulsed with ␣GalCer stimulate NKT cells through T cell receptor (TCR) ligation. 2,19,20 NKT cell activation and IFN-␥ production are markedly enhanced by DC-produced IL-12, with an increase in the IL-12 receptor on activated NKT cells. 15,21,22 Conversely, invariant NKT cells also interact with ␣Gal-Cer-loaded DCs to enhance CD4 ϩ and CD8 ϩ T-cell responses 16,17,23,24 and with B cells to provide help for antibody production. 25 However, ␣Galcer is not a physiological antigen, and it is not yet clear whether physiological NKT-DC interactions are mediated by specific CD1d-presented antigens or are antigen independent.The classical CD1d-reactive NKT cell population expresses a highly restricted TCR r...

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Impaired Proliferative Response of Vα24 NKT Cells from Cancer Patients Against α-Galactosylceramide

Cited by 121 publications

References 25 publications

Modulation of human Vα24+Vβ11+ NKT cells by age, malignancy and conventional anticancer therapies

Modulation of human Vα24+Vβ11+ NKT cells by age, malignancy and conventional anticancer therapies

Dendritic cell maturation by CD11c⁻ T cells and Vα24⁺ natural killer T‐cell activation by α‐Galactosylceramide

To be or not to be NKT: Natural killer T cells in the liver

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Impaired Proliferative Response of Vα24 NKT Cells from Cancer Patients Against α-Galactosylceramide

Cited by 121 publications

References 25 publications

Modulation of human Vα24+Vβ11+ NKT cells by age, malignancy and conventional anticancer therapies

Modulation of human Vα24+Vβ11+ NKT cells by age, malignancy and conventional anticancer therapies

Dendritic cell maturation by CD11c− T cells and Vα24+ natural killer T‐cell activation by α‐Galactosylceramide

To be or not to be NKT: Natural killer T cells in the liver

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Dendritic cell maturation by CD11c⁻ T cells and Vα24⁺ natural killer T‐cell activation by α‐Galactosylceramide