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 tumour cells. To fully harness the tumour killing ability of NK cells, we need to improve NK cell persistence and overcome suppression of NK cell activation in the tumour microenvironment. The trans-membrane, protein tyrosine phosphatase CD45, regulates NK cell homeostasis, with genetic loss of CD45 in mice resulting in increased numbers of mature NK cells [1–3]. This suggests that CD45-deficient NK cells might display enhanced persistence following adoptive transfer. However, here we demonstrated 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 common lymphoid 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 [4–6], 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.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviations
- NK
- Natural Killer
- PTP
- protein tyrosine phosphatase
- TCR
- T cell receptor
- BCR
- B cell receptor
- JAK
- Janus kinase
- Ig
- immunoglobulin
- IFN
- interferon
- PBS
- phosphate buffered saline
- BSA
- bovine serum albumin
- I.V.
- intravenous
- CTV
- CellTrace Violet
- BM
- bone marrow
- PI
- propidium iodide
- CRISPR
- Clustered Regularly Interspaced Short Palindromic Repeats
- FBS
- fetal bovine serum
- RT
- room temperature
- HSC
- hematopoietic stem cells
- LT-HSC
- long term HSC
- CLP
- common lymphoid progenitors
- MPP
- multipotent progenitor
- LMPP
- lymphoid primed MPPs
- HPC
- hematopoietic progenitor cell
- HSPC
- hematopoietic stem and progenitor cells