@article{376016268cd4447e9f321f66b5696437,
title = "CD45 limits early Natural Killer cell development",
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.",
keywords = "CD45, hematopoiesis, lymphocytes, Natural Killer cells, NK progenitor",
author = "\{Meza Guzman\}, \{Lizeth G.\} and Hyland, \{Craig D.\} and Bidgood, \{Grace M.\} and Evelyn Leong and Zihan Shen and Wilford Goh and Jai Rautela and Vince, \{James E.\} and Nicholson, \{Sandra E.\} and Huntington, \{Nicholas D.\}",
note = "Funding Information: The authors acknowledge the Wurundjeri people of the Kulin nation as the traditional owners and guardians of the land on which most of the work was performed. We thank Professor Warren Alexander for providing guidance and reagents, Professor Eric Vivier for providing Ncr1iCre mice and Dr Milon Pang for providing experimental advice. We thank Bioservices staff, Tania Camillari, Natasha Blasch and Sophia Russo, for mouse husbandry and injections. The Cd45 conditional knock out mice were produced via CRISPR/Cas9 oocyte injection by Monash University as a node of the Australian Phenomics Network (now Phenomics Australia), supported by the Australian Government Department of Education through the National Collaborative Research Infrastructure Strategy, the Super Science Initiative and the Collaborative Research Infrastructure Scheme. LGMG was supported by a Walter and Eliza Hall Institute International PhD Scholarship. GMB was supported by an Australian Government Research Training Program Scholarship. JEV was supported by a National Health and Medical Research Council (NHMRC) Investigator grant (GNT2008692) and NHMRC Ideas grants (1183070). NDH was supported by an NHMRC Investigator grant (GNT1195296) and NHMRC Project grants (GNT1124784, GNT1066770, GNT1057852, GNT1124907, GNT1057812, GNT1049407, GNT1027472, and GNT1184615, and is a recipient of a Melanoma Research Alliance Young Investigator Award, a National Foundation for Medical Research and Innovation (NFMRI) John Dixon Hughes Medal, and a Cancer Council of Victoria grant. This work was supported in part through Victorian State Government Operational Infrastructure Support and the Australian Government NHMRC Independent Research Institutes Infrastructure Support Scheme (IRIISS). Open access publishing facilitated by The University of Melbourne, as part of the Wiley - The University of Melbourne agreement via the Council of Australian University Librarians. Funding Information: The authors acknowledge the Wurundjeri people of the Kulin nation as the traditional owners and guardians of the land on which most of the work was performed. We thank Professor Warren Alexander for providing guidance and reagents, Professor Eric Vivier for providing Ncr1 mice and Dr Milon Pang for providing experimental advice. We thank Bioservices staff, Tania Camillari, Natasha Blasch and Sophia Russo, for mouse husbandry and injections. The conditional knock out mice were produced CRISPR/Cas9 oocyte injection by Monash University as a node of the Australian Phenomics Network (now Phenomics Australia), supported by the Australian Government Department of Education through the National Collaborative Research Infrastructure Strategy, the Super Science Initiative and the Collaborative Research Infrastructure Scheme. LGMG was supported by a Walter and Eliza Hall Institute International PhD Scholarship. GMB was supported by an Australian Government Research Training Program Scholarship. JEV was supported by a National Health and Medical Research Council (NHMRC) Investigator grant (GNT2008692) and NHMRC Ideas grants (1183070). NDH was supported by an NHMRC Investigator grant (GNT1195296) and NHMRC Project grants (GNT1124784, GNT1066770, GNT1057852, GNT1124907, GNT1057812, GNT1049407, GNT1027472, and GNT1184615, and is a recipient of a Melanoma Research Alliance Young Investigator Award, a National Foundation for Medical Research and Innovation (NFMRI) John Dixon Hughes Medal, and a Cancer Council of Victoria grant. This work was supported in part through Victorian State Government Operational Infrastructure Support and the Australian Government NHMRC Independent Research Institutes Infrastructure Support Scheme (IRIISS). Open access publishing facilitated by The University of Melbourne, as part of the Wiley ‐ The University of Melbourne agreement via the Council of Australian University Librarians. iCre Cd45 via Publisher Copyright: {\textcopyright} 2023 The Authors. Immunology \& Cell Biology published by John Wiley \& Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.",
year = "2024",
month = jan,
doi = "10.1111/imcb.12701",
language = "English",
volume = "102",
pages = "58--70",
journal = "Immunology and Cell Biology",
issn = "0818-9641",
publisher = "John Wiley \& Sons",
number = "1",
}
