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Hyperactive Natural Killer cells in Rag2 knockout mice inhibit the development of acute myeloid leukemia
- Source :
- Communications Biology, Vol 6, Iss 1, Pp 1-12 (2023)
- Publication Year :
- 2023
- Publisher :
- Nature Portfolio, 2023.
-
Abstract
- Abstract Immunotherapy has attracted considerable attention as a therapeutic strategy for cancers including acute myeloid leukemia (AML). In this study, we found that the development of several aggressive subtypes of AML is slower in Rag2 −/− mice despite the lack of B and T lymphocytes, even compared to the immunologically normal C57BL/6 mice. Furthermore, an orally active p53-activating drug shows stronger antileukemia effect on AML in Rag2 −/− mice than C57BL/6 mice. Intriguingly, Natural Killer (NK) cells in Rag2 −/− mice are increased in number, highly express activation markers, and show increased cytotoxicity to leukemia cells in a coculture assay. B2m depletion that triggers missing-self recognition of NK cells impairs the growth of AML cells in vivo. In contrast, NK cell depletion accelerates AML progression in Rag2 −/− mice. Interestingly, immunogenicity of AML keeps changing during tumor evolution, showing a trend that the aggressive AMLs generate through serial transplantations are susceptible to NK cell-mediated tumor suppression in Rag2 −/− mice. Thus, we show the critical role of NK cells in suppressing the development of certain subtypes of AML using Rag2 −/− mice, which lack functional lymphocytes but have hyperactive NK cells.
- Subjects :
- Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 23993642
- Volume :
- 6
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Communications Biology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.5b6b8d5e72fb4e78b3b3547dd6332877
- Document Type :
- article
- Full Text :
- https://doi.org/10.1038/s42003-023-05606-3