自然杀伤 (NK) 细胞在先天免疫中发挥着至关重要的作用，特别是在对抗感染和肿瘤方面。然而，在血液癌症中，NK 细胞常常表现出功能受损。因此，激活其内体Toll样受体（TLR）作为恢复其抗肿瘤活性的潜在策略非常重要。我们刺激来自急性淋巴细胞白血病儿童的外周血单核细胞和分离的 NK 细胞的 NK 细胞，并用特定的 TLR 配体（Poly I:C、咪喹莫特、R848 和 ODN2006）刺激 NK 细胞，并评估 IFN 的变化-γ、CD107a、NKG2D、NKp44 表达、颗粒酶 B 分泌、细胞因子/趋化因子释放和细胞毒活性。结果显示，Poly I:C 和咪喹莫特增强了免疫调节和细胞毒性 NK 细胞的激活，增加了 IFN-γ、CD107a、NKG2D 和 NKp44 的表达。 R848 激活免疫调节 NK 细胞，而 ODN2006 增强细胞毒性 NK 细胞中 CD107a、NKp44、NKG2D 和 IFN-γ 的分泌。 R848 还增加了七种细胞因子/趋化因子的分泌。重要的是，R848 和 ODN 2006 显着提高了针对白血病细胞的细胞毒性。总体而言，TLR 刺激可增强 NK 细胞活化，表明 TLR8 (R848) 和 TLR9 (ODN 2006) 配体是抗肿瘤免疫治疗的有希望的候选物。

Natural killer (NK) cells play a crucial role in innate immunity, particularly in combating infections and tumors. However, in hematological cancers, NK cells often exhibit impaired functions. Therefore, it is very important to activate its endosomal Toll-like receptors (TLRs) as a potential strategy to restore its antitumor activity. We stimulated NK cells from the peripheral blood mononuclear cells from children with acute lymphoblastic leukemia and NK cells isolated, and the NK cells were stimulated with specific TLR ligands (Poly I:C, Imiquimod, R848, and ODN2006) and we evaluated changes in IFN-γ, CD107a, NKG2D, NKp44 expression, Granzyme B secretion, cytokine/chemokine release, and cytotoxic activity. Results revealed that Poly I:C and Imiquimod enhanced the activation of both immunoregulatory and cytotoxic NK cells, increasing IFN-γ, CD107a, NKG2D, and NKp44 expression. R848 activated immunoregulatory NK cells, while ODN2006 boosted CD107a, NKp44, NKG2D, and IFN-γ secretion in cytotoxic NK cells. R848 also increased the secretion of seven cytokines/chemokines. Importantly, R848 and ODN 2006 significantly improved cytotoxicity against leukemic cells. Overall, TLR stimulation enhances NK cell activation, suggesting TLR8 (R848) and TLR9 (ODN 2006) ligands as promising candidates for antitumor immunotherapy.