CD45 limits early Natural Killer cell development
- Author(s)
- Meza Guzman, LG; Hyland, CD; Bidgood, GM; Leong, E; Shen, Z; Goh, W; Rautela, J; Vince, JE; Nicholson, SE; Huntington, ND;
- Journal Title
- Immmunology and Cell Biology
- Publication Type
- epub ahead of print
- Abstract
- The clinical development of Natural Killer (NK) cell-mediated immunotherapy marks a milestone in the development of new cancer therapies and has gained traction due to the intrinsic ability of the NK cell to target and kill tumor cells. To fully harness the tumor killing ability of NK cells, we need to improve NK cell persistence and to overcome suppression of NK cell activation in the tumor microenvironment. The trans-membrane, protein tyrosine phosphatase CD45, regulates NK cell homeostasis, with the genetic loss of CD45 in mice resulting in increased numbers of mature NK cells. This suggests that CD45-deficient NK cells might display enhanced persistence following adoptive transfer. However, we demonstrate here that adoptive transfer of CD45-deficiency did not enhance NK cell persistence in mice, and instead, the homeostatic disturbance of NK cells in CD45-deficient mice stemmed from a developmental defect in the progenitor population. The enhanced maturation within the CD45-deficient NK cell compartment was intrinsic to the NK cell lineage, and independent of the developmental defect. CD45 is not a conventional immune checkpoint candidate, as systemic loss is detrimental to T and B cell development, compromising the adaptive immune system. Nonetheless, this study suggests that inhibition of CD45 in progenitor or stem cell populations may improve the yield of in vitro generated NK cells for adoptive therapy.
- Publisher
- Wiley
- Keywords
- Cd45; NK progenitor; Natural Killer cells; hematopoiesis; lymphocytes
- Research Division(s)
- Inflammation; Blood Cells And Blood Cancer
- PubMed ID
- 37855066
- Publisher's Version
- https://doi.org/10.1111/imcb.12701
- Open Access at Publisher's Site
https://doi.org/10.1111/imcb.12701- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-11-15 05:00:14
Last Modified: 2023-11-15 05:33:32