| Title |
The role of interleukin-2, all-trans retinoic acid, and natural killer cells: surveillance mechanisms in anti-GD2 antibody therapy in neuroblastoma
|
|---|---|
| Published in |
Cancer Immunology, Immunotherapy, January 2018
|
| DOI | 10.1007/s00262-017-2108-6 |
| Pubmed ID | |
| Authors |
Rosa Nguyen, Jim Houston, Wing K. Chan, David Finkelstein, Michael A. Dyer |
| Abstract |
Although anti-disialoganglioside (GD2) antibodies are successfully used for neuroblastoma therapy, a third of patients with neuroblastoma experience treatment failure or serious toxicity. Various strategies have been employed in the clinic to improve antibody-dependent cell-mediated cytotoxicity (ADCC), such as the addition of interleukin (IL)-2 to enhance natural killer (NK) cell function, adoptive transfer of allogeneic NK cells to exploit immune surveillance, and retinoid-induced differentiation therapy. Nevertheless, these mechanisms are not fully understood. We developed a quantitative assay to test ADCC induced by the anti-GD2 antibody Hu14.18K322A in nine neuroblastoma cell lines and dissociated cells from orthotopic patient-derived xenografts (O-PDXs) in culture. IL-2 improved ADCC against neuroblastoma cells, and differentiation with all-trans retinoic acid stabilized GD2 expression on tumor cells and enhanced ADCC as well. Degranulation was highest in licensed NK cells that expressed CD158b (P < 0.001) and harbored a killer-cell immunoglobulin-like receptor (KIR) mismatch against the tumor-specific human leukocyte antigen (HLA; P = 0.016). In conclusion, IL-2 is an important component of immunotherapy because it can improve the cytolytic function of NK cells against neuroblastoma cells and could lower the antibody dose required for efficacy, thereby reducing toxicity. The effect of IL-2 may vary among individuals and a biomarker would be useful to predict ADCC following IL-2 activation. Sub-populations of NK cells may have different levels of activity dependent on their licensing status, KIR expression, and HLA-KIR interaction. Better understanding of HLA-KIR interactions and the molecular changes following retinoid-induced differentiation is necessary to delineate their role in ADCC. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 3 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 37 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 9 | 24% |
| Student > Bachelor | 5 | 14% |
| Student > Ph. D. Student | 4 | 11% |
| Researcher | 2 | 5% |
| Librarian | 2 | 5% |
| Other | 5 | 14% |
| Unknown | 10 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 7 | 19% |
| Medicine and Dentistry | 5 | 14% |
| Agricultural and Biological Sciences | 4 | 11% |
| Immunology and Microbiology | 3 | 8% |
| Environmental Science | 1 | 3% |
| Other | 5 | 14% |
| Unknown | 12 | 32% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 February 2018.
All research outputs
#14,963,216
of 23,016,919 outputs
Outputs from Cancer Immunology, Immunotherapy
#2,073
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Outputs of similar age
#256,719
of 443,312 outputs
Outputs of similar age from Cancer Immunology, Immunotherapy
#20
of 31 outputs
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