肿瘤细胞治疗研究
英文原题：Overcoming CD226-related immune evasion in acute myeloid leukemia with CD38 CAR-engineered NK cells.
我们的研究结果表明，CAR38 NK 细胞可能是克服急性髓系白血病中 CD226 介导的免疫逃逸的有效治疗策略。
CD226在自然杀伤（NK）细胞细胞毒作用中发挥关键作用；其与配体CD112和CD155相互作用，主要通过白细胞功能相关抗原1（LFA-1）启动免疫突触形成。本研究考察CD226在NK细胞监视急性髓系白血病（AML）中的作用。AML患者的NK细胞CD226表达较低。采用CRISPR-Cas9敲除CD226会减少LFA-1募集、损害免疫突触形成并降低NK细胞抗白血病活性。通过工程化改造NK细胞，使其表达靶向AML抗原CD38的嵌合抗原受体（CAR38），可克服建立强效免疫突触对CD226的依赖。阻断LFA-1会降低CAR38 NK细胞活性，且这一效应取决于AML细胞的CD38表达水平。这提示LFA-1和CAR38在免疫突触形成中具有平行但可能协同的作用。研究结果提示，CAR38 NK细胞可能成为克服AML中CD226介导免疫逃逸的有效治疗策略。
CD226 plays a vital role in natural killer (NK) cell cytotoxicity, interacting with its ligands CD112 and CD155 to initiate immune synapse formation, primarily through leukocyte function-associated-1 (LFA-1). Our study examined the role of CD226 in NK cell surveillance of acute myeloid leukemia (AML). NK cells in patients with AML had lower expression of CD226. CRISPR-Cas9 deletion of CD226 led to reduced LFA-1 recruitment, poor synapse formation, and decreased NK cell anti-leukemic activity. Engineering NK cells to express a chimeric antigen receptor targeting the AML antigen CD38 (CAR38) could overcome the need for CD226 to establish strong immune synapses. LFA-1 blockade reduced CAR38 NK cell activity, and this depended on the CD38 expression levels of AML cells. This suggests parallel but potentially cooperative roles for LFA-1 and CAR38 in synapse formation. Our findings suggest that CAR38 NK cells could be an effective therapeutic strategy to overcome CD226-mediated immune evasion in AML.
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