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Invariant NKT cells are resistant to circulating CD15+ myeloid-derived suppressor cells in patients with head and neck cancer.

Horinaka A, Sakurai D, Ihara F, Makita Y, Kunii N, Motohashi S, Nakayama T, Okamoto Y - Cancer Sci. (2016)

Bottom Line: However, the effect on the host immune system, especially on invariant NKT (iNKT) cells with potent anti-tumor activity, remains unclear.However, iNKT cell activation upon α-galactosylceramide (αGalCer) stimulation was not affected by the presence or absence of CD15+ G-MDSC.Cancer immunotherapy designed to enhance the antitumor activity of iNKT cells by stimulation with αGalCer may remain effective in the presence of G-MDSC.

View Article: PubMed Central - PubMed

Affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.

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Related in: MedlinePlus

Invariant NKT (iNKT) cells are resistant to granulocytic‐myeloid‐derived suppressor cells (G‐MDSC). (a) The percentage of CD15+ cells in the HLA‐DR− Lin− fraction of whole peripheral blood cells (PBC) from a head and neck squamous cell carcinoma (HNSCC) patient before (left) and after (right) depletion by CD15 magnetic beads. PBC with and without CD15+ cells were cultured for 5 days, stimulated with αGalCer. (b–e) The cell numbers were counted, and the staining profile, percentage of cell death and apoptosis of iNKT cells were assessed by flow cytometry. (f) IFN‐γ produced by iNKT cells was assessed by ELISPOT after 5 days. NS, not significant.
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cas12866-fig-0006: Invariant NKT (iNKT) cells are resistant to granulocytic‐myeloid‐derived suppressor cells (G‐MDSC). (a) The percentage of CD15+ cells in the HLA‐DR− Lin− fraction of whole peripheral blood cells (PBC) from a head and neck squamous cell carcinoma (HNSCC) patient before (left) and after (right) depletion by CD15 magnetic beads. PBC with and without CD15+ cells were cultured for 5 days, stimulated with αGalCer. (b–e) The cell numbers were counted, and the staining profile, percentage of cell death and apoptosis of iNKT cells were assessed by flow cytometry. (f) IFN‐γ produced by iNKT cells was assessed by ELISPOT after 5 days. NS, not significant.

Mentions: We evaluated the proliferation and viability of iNKT cells and IFN‐γ production following stimulation with αGalCer in the presence or absence of CD15+ cells. In a representative HNSCC patient, the CD15+ cells comprised 15.8% of the HLA‐DR− Lin− fraction in PBC, and after CD15+ cell depletion, only 0.01% were positive (Fig. 6a). There was no significant difference in the cell number (Fig. 6b), the ratio in PBC (Fig. 6c) and the cell death in iNKT cells (Fig. 6d,e) between CD15+ cell replete cultures and CD15+ cell‐depleted cultures after 5 days. There was no significant difference in the IFN‐γ production of iNKT cells between non‐depleted and CD15+ cell‐depleted cultures after 5 days (Fig. 6f). Similarly, 5 days after stimulation with αGalCer, there was no difference in iNKT cell number between CD15+ cell‐depleted and CD15+ cell‐added PBC (Fig. 5f). These results were repeated in three samples.


Invariant NKT cells are resistant to circulating CD15+ myeloid-derived suppressor cells in patients with head and neck cancer.

Horinaka A, Sakurai D, Ihara F, Makita Y, Kunii N, Motohashi S, Nakayama T, Okamoto Y - Cancer Sci. (2016)

Invariant NKT (iNKT) cells are resistant to granulocytic‐myeloid‐derived suppressor cells (G‐MDSC). (a) The percentage of CD15+ cells in the HLA‐DR− Lin− fraction of whole peripheral blood cells (PBC) from a head and neck squamous cell carcinoma (HNSCC) patient before (left) and after (right) depletion by CD15 magnetic beads. PBC with and without CD15+ cells were cultured for 5 days, stimulated with αGalCer. (b–e) The cell numbers were counted, and the staining profile, percentage of cell death and apoptosis of iNKT cells were assessed by flow cytometry. (f) IFN‐γ produced by iNKT cells was assessed by ELISPOT after 5 days. NS, not significant.
© Copyright Policy - creativeCommonsBy-nc-nd
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4814259&req=5

cas12866-fig-0006: Invariant NKT (iNKT) cells are resistant to granulocytic‐myeloid‐derived suppressor cells (G‐MDSC). (a) The percentage of CD15+ cells in the HLA‐DR− Lin− fraction of whole peripheral blood cells (PBC) from a head and neck squamous cell carcinoma (HNSCC) patient before (left) and after (right) depletion by CD15 magnetic beads. PBC with and without CD15+ cells were cultured for 5 days, stimulated with αGalCer. (b–e) The cell numbers were counted, and the staining profile, percentage of cell death and apoptosis of iNKT cells were assessed by flow cytometry. (f) IFN‐γ produced by iNKT cells was assessed by ELISPOT after 5 days. NS, not significant.
Mentions: We evaluated the proliferation and viability of iNKT cells and IFN‐γ production following stimulation with αGalCer in the presence or absence of CD15+ cells. In a representative HNSCC patient, the CD15+ cells comprised 15.8% of the HLA‐DR− Lin− fraction in PBC, and after CD15+ cell depletion, only 0.01% were positive (Fig. 6a). There was no significant difference in the cell number (Fig. 6b), the ratio in PBC (Fig. 6c) and the cell death in iNKT cells (Fig. 6d,e) between CD15+ cell replete cultures and CD15+ cell‐depleted cultures after 5 days. There was no significant difference in the IFN‐γ production of iNKT cells between non‐depleted and CD15+ cell‐depleted cultures after 5 days (Fig. 6f). Similarly, 5 days after stimulation with αGalCer, there was no difference in iNKT cell number between CD15+ cell‐depleted and CD15+ cell‐added PBC (Fig. 5f). These results were repeated in three samples.

Bottom Line: However, the effect on the host immune system, especially on invariant NKT (iNKT) cells with potent anti-tumor activity, remains unclear.However, iNKT cell activation upon α-galactosylceramide (αGalCer) stimulation was not affected by the presence or absence of CD15+ G-MDSC.Cancer immunotherapy designed to enhance the antitumor activity of iNKT cells by stimulation with αGalCer may remain effective in the presence of G-MDSC.

View Article: PubMed Central - PubMed

Affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.

Show MeSH
Related in: MedlinePlus