| First Author | Sugimoto E | Year | 2023 |
| Journal | Commun Biol | Volume | 6 |
| Issue | 1 | Pages | 1294 |
| PubMed ID | 38129572 | Mgi Jnum | J:351852 |
| Mgi Id | MGI:7568166 | Doi | 10.1038/s42003-023-05606-3 |
| Citation | Sugimoto E, et al. (2023) Hyperactive Natural Killer cells in Rag2 knockout mice inhibit the development of acute myeloid leukemia. Commun Biol 6(1):1294 |
| abstractText | 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. |
