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Abstract：
The interaction of the tumor necrosis factor receptor (TNFR) family member CD27 on naive CD8+ T (Tn) cells with homotrimeric CD70 on antigen-presenting cells (APCs) is necessary for T cell memory fate determination. Here, we examined CD27 signaling during Tn cell activation and differentiation. In conjunction with T cell receptor (TCR) stimulation, ligation of CD27 by a synthetic trimeric CD70 ligand triggered CD27 internalization and degradation, suggesting active regulation of this signaling axis. Internalized CD27 recruited the signaling adaptor TRAF2 and the phosphatase SHP-1, thereby modulating TCR and CD28 signals. CD27-mediated modulation of TCR signals promoted transcription factor circuits that induced memory rather than effector associated gene programs, which are induced by CD28 costimulation. CD27-costimulated chimeric antigen receptor (CAR)-engineered T cells exhibited improved tumor control compared with CD28-costimulated CAR-T cells. Thus, CD27 signaling during Tn cell activation promotes memory properties with relevance to T cell immunotherapy.
摘要：
幼稚CD8T（Tn）细胞上的肿瘤坏死因子受体（TNFR）家族成员CD27与抗原呈递细胞（APC）上的同源三聚体CD70的相互作用对于确定T细胞记忆命运是必需的。这里,我们检查了Tn细胞活化和分化过程中的CD27信号传导。结合T细胞受体（TCR）刺激，通过合成三聚体CD70配体连接CD27触发CD27内化和降解，表明该信号轴的主动调节。内化的CD27募集信号接头TRAF2和磷酸酶SHP-1，从而调节TCR和CD28信号。CD27介导的TCR信号调节促进转录因子回路，诱导记忆，而不是效应相关的基因程序，由CD28共刺激诱导。与CD28共刺激的CAR-T细胞相比，CD27共刺激的嵌合抗原受体（CAR）工程化的T细胞表现出改善的肿瘤对照。因此，Tn细胞活化期间的CD27信号传导促进与T细胞免疫疗法相关的记忆特性。
