PDF(Pubmed)
Abstract：
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.
摘要：
自然杀伤（NK）细胞在先天免疫中起着至关重要的作用，特别是在对抗感染和肿瘤方面。然而,在血液癌症中，NK细胞通常表现出受损的功能。因此,激活其内体Toll样受体（TLRs）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患儿外周血单核细胞的NK细胞，并用特定的TLR配体刺激NK细胞（PolyI：C，咪喹莫特,R848和ODN2006)，我们评估了IFN-γ的变化，CD107a,NKG2D,NKp44表达式，颗粒酶B分泌，细胞因子/趋化因子释放，和细胞毒活性。结果表明，PolyI：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IFN-γ，CD107a,NKG2D,和NKp44表达。R848激活免疫调节NK细胞，而ODN2006提高了CD107a，NKp44,NKG2D,和细胞毒性NK细胞中的IFN-γ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ODN2006显著提高了对白血病细胞的细胞毒性。总的来说,TLR刺激增强NK细胞活化,提示TLR8（R848）和TLR9（ODN2006）配体是抗肿瘤免疫疗法的有希望的候选者。
