Abstract | BACKGROUND:
IRX-2 is a primary biologic which has been used for the therapy of head and neck squamous cell cancer ( HNSCC) with promising clinical results. Since NK-cell function is compromised in HNSCC patients, we tested the effects of IRX-2 on the restoration of human NK-cell functions in vitro. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from 23 HNSCC patients and 10 normal controls (NC). The NK-cell phenotype and functions were compared before and after culture ± IRX-2 or ± 50 IU/ml rhIL-2. Flow cytometry was used to study the NK-cell phenotype, cytotoxic activity and cytokine expression. RESULTS: Impaired NK-cell cytotoxicity in HNSCC patients was related to lower expression of NKG2D, NKp30 and NKp46 receptors (P < 0.05) and not to a decreased frequency of NK cells. Incubation of patients' NK cells with IRX-2 up-regulated the percentage of receptor-positive NK cells (P < 0.05). It also up-regulated cytotoxicity of patients' NK cells (P < 0.01) more effectively than rhIL-2 (P < 0.01). IRX-2, but not rhIL-2, protected NK cells from suppression mediated by TGF-β, and it restored (P < 0.05) expression of activating NK-cell receptors and NK-cell cytotoxicity suppressed by TGF-β. Expression of pSMAD was decreased in NK cells treated with IRX-2 but not in those treated with rhIL-2. CONCLUSIONS:
IRX-2 was more effective than IL-2 in enhancing NK-cell cytotoxicity and protecting NK-cell function of HNSCC patients in vitro, emphasizing the potential advantage of IRX-2 as a component of future therapies for HNSCC.
|
Authors | B Schilling, E S Halstead, P Schuler, M Harasymczuk, J E Egan, T L Whiteside |
Journal | Cancer immunology, immunotherapy : CII
(Cancer Immunol Immunother)
Vol. 61
Issue 9
Pg. 1395-405
(Sep 2012)
ISSN: 1432-0851 [Electronic] Germany |
PMID | 22270713
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
|
Chemical References |
- Cytokines
- IRX 2
- Interleukin-2
- KLRK1 protein, human
- NCR1 protein, human
- NCR3 protein, human
- NK Cell Lectin-Like Receptor Subfamily K
- Natural Cytotoxicity Triggering Receptor 1
- Natural Cytotoxicity Triggering Receptor 3
- Smad Proteins
- Transforming Growth Factor beta1
|
Topics |
- Carcinoma, Squamous Cell
(blood, immunology, therapy)
- Cytokines
(immunology, pharmacology)
- Cytotoxicity, Immunologic
(drug effects, immunology)
- Flow Cytometry
- Head and Neck Neoplasms
(blood, immunology, therapy)
- Humans
- Immunotherapy
- Interleukin-2
(immunology, pharmacology)
- K562 Cells
- Killer Cells, Natural
(drug effects, immunology)
- Leukocytes, Mononuclear
(drug effects, immunology)
- NK Cell Lectin-Like Receptor Subfamily K
(biosynthesis, immunology)
- Natural Cytotoxicity Triggering Receptor 1
(biosynthesis, immunology)
- Natural Cytotoxicity Triggering Receptor 3
(biosynthesis, immunology)
- Phosphorylation
(drug effects)
- Smad Proteins
(biosynthesis, immunology)
- Transforming Growth Factor beta1
(immunology, pharmacology)
- Up-Regulation
(drug effects, immunology)
|