| First Author | Deuse T | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 3 | PubMed ID | 33416832 |
| Mgi Jnum | J:307806 | Mgi Id | MGI:6509834 |
| Doi | 10.1084/jem.20200839 | Citation | Deuse T, et al. (2021) The SIRPalpha-CD47 immune checkpoint in NK cells. J Exp Med 218(3) |
| abstractText | Here we report on the existence and functionality of the immune checkpoint signal regulatory protein alpha (SIRPalpha) in NK cells and describe how it can be modulated for cell therapy. NK cell SIRPalpha is up-regulated upon IL-2 stimulation, interacts with target cell CD47 in a threshold-dependent manner, and counters other stimulatory signals, including IL-2, CD16, or NKG2D. Elevated expression of CD47 protected K562 tumor cells and mouse and human MHC class I-deficient target cells against SIRPalpha+ primary NK cells, but not against SIRPalpha- NKL or NK92 cells. SIRPalpha deficiency or antibody blockade increased the killing capacity of NK cells. Overexpression of rhesus monkey CD47 in human MHC-deficient cells prevented cytotoxicity by rhesus NK cells in a xenogeneic setting. The SIRPalpha-CD47 axis was found to be highly species specific. Together, the results demonstrate that disruption of the SIRPalpha-CD47 immune checkpoint may augment NK cell antitumor responses and that elevated expression of CD47 may prevent NK cell-mediated killing of allogeneic and xenogeneic tissues. |
