Hyperactive Natural Killer cells in Rag2 knockout mice inhibit the development of acute myeloid leukemia.

Autor: Sugimoto, Emi, Li, Jingmei, Hayashi, Yasutaka, Iida, Kohei, Asada, Shuhei, Fukushima, Tsuyoshi, Tamura, Moe, Shikata, Shiori, Zhang, Wenyu, Yamamoto, Keita, Kawabata, Kimihito Cojin, Kawase, Tatsuya, Saito, Takeshi, Yoshida, Taku, Yamazaki, Satoshi, Kaito, Yuta, Imai, Yoichi, Denda, Tamami, Ota, Yasunori, Fukuyama, Tomofusa
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Zdroj: Communications Biology; 12/21/2023, Vol. 6 Issue 1, p1-12, 12p
Abstrakt: 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. Natural Killer (NK) cells play a role in suppressing the development of certain subtypes of acute myeloid leukemia as shown by employing Rag2−/− mice as model system, which lack functional lymphocytes but have hyperactive NK cells. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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