Abstract
Augmentation of natural killer (NK) cell cytotoxicity is one of the greatest challenges for cancer immunotherapy. Although histidine-rich glycoprotein (HRG), a 75-kDa glycoprotein with various immunomodulatory activities, reportedly elicits antitumor immunity, its effect on NK cell cytotoxicity is unclear. We assessed NK cell cytotoxicity against K562 cells. We also measured concentrations of cytokines and granzyme B in the cell supernatant. The proportion of CD56bright NK cells and NK cell surface PD-1 expression was assessed with flow cytometry. The neutralizing effects of anti-C-type lectin-like receptor (CLEC) 1B against HRG were also measured. NK cell morphological changes were analyzed via confocal microscopy. HRG significantly increased NK cell cytotoxicity against K562 cell lines. HRG also increased the release of granzyme B and the proportion of CD56bright NK cells. Further, HRG was able to decrease NK cell surface PD-1 expression. The effects of HRG on NK cells were reversed with anti-CLEC-1B antibodies. Additionally, we confirmed NK cell nuclear morphology and F-actin distribution, which are involved in the regulation of cytotoxic granule secretion. Because both PD-1 and CLEC-1B are associated with prognosis during malignancy, HRG incorporates these molecules to exert the antitumor immunity role. These facts indicate the potential of HRG to be a new target for cancer immunotherapy.
| Original language | English |
|---|---|
| Article number | e00481 |
| Journal | Pharmacology Research and Perspectives |
| Volume | 7 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Jun 1 2019 |
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Keywords
- C-type lectin-like receptor
- histidine-rich glycoprotein
- natural killer cell
- programmed-death-1
ASJC Scopus subject areas
- Neurology
- Pharmacology, Toxicology and Pharmaceutics(all)
Cite this
Histidine-rich glycoprotein augments natural killer cell function by modulating PD-1 expression via CLEC-1B. / Nishimura, Yoshito; Wake, Hidenori; Teshigawara, Kiyoshi; Wang, Dengli; Sakaguchi, Masakiyo; Otsuka, Fumio; Nishibori, Masahiro.
In: Pharmacology Research and Perspectives, Vol. 7, No. 3, e00481, 01.06.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Histidine-rich glycoprotein augments natural killer cell function by modulating PD-1 expression via CLEC-1B
AU - Nishimura, Yoshito
AU - Wake, Hidenori
AU - Teshigawara, Kiyoshi
AU - Wang, Dengli
AU - Sakaguchi, Masakiyo
AU - Otsuka, Fumio
AU - Nishibori, Masahiro
PY - 2019/6/1
Y1 - 2019/6/1
N2 - Augmentation of natural killer (NK) cell cytotoxicity is one of the greatest challenges for cancer immunotherapy. Although histidine-rich glycoprotein (HRG), a 75-kDa glycoprotein with various immunomodulatory activities, reportedly elicits antitumor immunity, its effect on NK cell cytotoxicity is unclear. We assessed NK cell cytotoxicity against K562 cells. We also measured concentrations of cytokines and granzyme B in the cell supernatant. The proportion of CD56bright NK cells and NK cell surface PD-1 expression was assessed with flow cytometry. The neutralizing effects of anti-C-type lectin-like receptor (CLEC) 1B against HRG were also measured. NK cell morphological changes were analyzed via confocal microscopy. HRG significantly increased NK cell cytotoxicity against K562 cell lines. HRG also increased the release of granzyme B and the proportion of CD56bright NK cells. Further, HRG was able to decrease NK cell surface PD-1 expression. The effects of HRG on NK cells were reversed with anti-CLEC-1B antibodies. Additionally, we confirmed NK cell nuclear morphology and F-actin distribution, which are involved in the regulation of cytotoxic granule secretion. Because both PD-1 and CLEC-1B are associated with prognosis during malignancy, HRG incorporates these molecules to exert the antitumor immunity role. These facts indicate the potential of HRG to be a new target for cancer immunotherapy.
AB - Augmentation of natural killer (NK) cell cytotoxicity is one of the greatest challenges for cancer immunotherapy. Although histidine-rich glycoprotein (HRG), a 75-kDa glycoprotein with various immunomodulatory activities, reportedly elicits antitumor immunity, its effect on NK cell cytotoxicity is unclear. We assessed NK cell cytotoxicity against K562 cells. We also measured concentrations of cytokines and granzyme B in the cell supernatant. The proportion of CD56bright NK cells and NK cell surface PD-1 expression was assessed with flow cytometry. The neutralizing effects of anti-C-type lectin-like receptor (CLEC) 1B against HRG were also measured. NK cell morphological changes were analyzed via confocal microscopy. HRG significantly increased NK cell cytotoxicity against K562 cell lines. HRG also increased the release of granzyme B and the proportion of CD56bright NK cells. Further, HRG was able to decrease NK cell surface PD-1 expression. The effects of HRG on NK cells were reversed with anti-CLEC-1B antibodies. Additionally, we confirmed NK cell nuclear morphology and F-actin distribution, which are involved in the regulation of cytotoxic granule secretion. Because both PD-1 and CLEC-1B are associated with prognosis during malignancy, HRG incorporates these molecules to exert the antitumor immunity role. These facts indicate the potential of HRG to be a new target for cancer immunotherapy.
KW - C-type lectin-like receptor
KW - histidine-rich glycoprotein
KW - natural killer cell
KW - programmed-death-1
UR - http://www.scopus.com/inward/record.url?scp=85066924730&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066924730&partnerID=8YFLogxK
U2 - 10.1002/prp2.481
DO - 10.1002/prp2.481
M3 - Article
C2 - 31143450
AN - SCOPUS:85066924730
VL - 7
JO - Pharmacology Research and Perspectives
JF - Pharmacology Research and Perspectives
SN - 2052-1707
IS - 3
M1 - e00481
ER -