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- The SIRPα-CD47 immune checkpoint in NK cells.
The SIRPα-CD47 immune checkpoint in NK cells.
Citation | “The Sirpα-Cd47 Immune Checkpoint In Nk Cells.”. The Journal Of Experimental Medicine. . |
Author | Tobias Deuse, Xiaomeng Hu, Sean Agbor-Enoh, Moon K Jang, Malik Alawi, Ceren Saygi, Alessia Gravina, Grigol Tediashvili, Vinh Q Nguyen, Yuan Liu, Hannah Valantine, Lewis L Lanier, Sonja Schrepfer |
Abstract |
Here we report on the existence and functionality of the immune checkpoint signal regulatory protein α (SIRPα) in NK cells and describe how it can be modulated for cell therapy. NK cell SIRPα 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 SIRPα+ primary NK cells, but not against SIRPα- NKL or NK92 cells. SIRPα 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 SIRPα-CD47 axis was found to be highly species specific. Together, the results demonstrate that disruption of the SIRPα-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. |
Year of Publication |
2021
|
Journal |
The Journal of experimental medicine
|
Volume |
218
|
Issue |
3
|
Date Published |
03/2021
|
ISSN Number |
1540-9538
|
DOI |
10.1084/jem.20200839
|
Alternate Journal |
J Exp Med
|
PMID |
33416832
|
PMCID |
PMC7802363
|
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