肿瘤细胞治疗研究
英文原题：GATA1-mediated Notch signaling augment antitumor immunity of CD11b(+)CD27(-) natural killer cells maturation via BCL9/β-catenin signal.
自然杀伤（NK）细胞的成熟过程对其抗肿瘤免疫应答至关重要。
自然杀伤（NK）细胞的成熟过程是其抗肿瘤免疫应答的重要组成部分。尽管NK细胞在分化期间展现多种效应特性，针对其命运进行免疫治疗仍具挑战。本研究显示，B细胞淋巴瘤9（BCL9）缺失可在Notch和白细胞介素-18受体1（IL-18R1）信号激活后，诱导CD11b+ CD27− NK细胞短暂表达GATA1；这些信号对NK细胞成熟和抗肿瘤活性至关重要。相反，阻断Notch信号会损害NK细胞发育及抗肿瘤功能。NK细胞特异性Bcl9缺失可增强体内对B16F10肿瘤的杀伤。本研究结果凸显了转录因子、发育过程中的信号转导通路及BCL9缺失所调控细胞因子之间复杂的网络相互作用。靶向BCL9有望成为黑色素瘤治疗策略，可促进NK细胞成熟和细胞毒活性，并克服NK细胞疗法面临的挑战。
The maturation process of natural killer (NK) cells is integral to their antitumor immune response. Despite the diverse effector properties exhibited during differentiation, targeting the fate of NK cells for immunotherapy remains challenging. Here, we demonstrate that deficiency of B cell lymphoma 9 (BCL9) induces transient expression of GATA1 in CD11b + CD27 - NK cells upon activation of Notch and interleukin-18 receptor 1 (IL-18R1) signaling, which are crucial for their maturation and antitumor activity. Conversely, blocking Notch signaling impairs NK cell development and antitumor function. NK-specific Bcl9-deficiency enhances B16F10 tumor killing in vivo. Our findings underscore the intricate network interactions among transcription factors, signal transduction pathways in development, and cytokines modulated by BCL9 deficiency. Targeting BCL9 emerges as a promising strategy for melanoma therapy, bolstering NK cell maturation and cytotoxicity, and overcoming challenges in NK cell-based immunotherapies.
MEMBER ACCOUNT
登录成功会直接打开下一页。
