Papers

International journal
Jun, 2019

Histidine-rich glycoprotein augments natural killer cell function by modulating PD-1 expression via CLEC-1B.

Pharmacology research & perspectives
  • Yoshito Nishimura
  • ,
  • Hidenori Wake
  • ,
  • Kiyoshi Teshigawara
  • ,
  • Dengli Wang
  • ,
  • Masakiyo Sakaguchi
  • ,
  • Fumio Otsuka
  • ,
  • Masahiro Nishibori

Volume
7
Number
3
First page
e00481
Last page
e00481
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1002/prp2.481
Publisher
JOHN WILEY & SONS LTD

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.

Link information
DOI
https://doi.org/10.1002/prp2.481
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31143450
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531599
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000470825600010&DestApp=WOS_CPL
ID information
  • DOI : 10.1002/prp2.481
  • ISSN : 2052-1707
  • Pubmed ID : 31143450
  • Pubmed Central ID : PMC6531599
  • Web of Science ID : WOS:000470825600010

Export
BibTeX RIS