PDF(Pubmed)
Abstract：
Tumor recurrence after chemoradiotherapy is challenging to overcome, and approaches to predict the recurrence remain elusive. Here, human cervical cancer tissues before and after concurrent chemoradiotherapy (CCRT) analyzed by single-cell RNA sequencing reveal that CCRT specifically promotes CD8+ T cell senescence, driven by atypical chemokine receptor 2 (ACKR2)+ CCRT-resistant tumor cells. Mechanistically, ACKR2 expression is increased in response to CCRT and is also upregulated through the ligation of CC chemokines that are produced by activated myeloid and T cells. Subsequently, ACKR2+ tumor cells are induced to produce transforming growth factor β to drive CD8+ T cell senescence, thereby compromising antitumor immunity. Moreover, retrospective analysis reveals that ACKR2 expression and CD8+ T cell senescence are enhanced in patients with cervical cancer who experienced recurrence after CCRT, indicating poor prognosis. Overall, we identify a subpopulation of CCRT-resistant ACKR2+ tumor cells driving CD8+ T cell senescence and tumor recurrence and highlight the prognostic value of ACKR2 and CD8+ T cell senescence for chemoradiotherapy recurrence.
摘要：
放化疗后的肿瘤复发是具有挑战性的克服，预测复发的方法仍然难以捉摸。这里,通过单细胞RNA测序分析同步放化疗（CCRT）前后的人宫颈癌组织显示，CCRT特异性促进CD8+T细胞衰老，由非典型趋化因子受体2（ACKR2）+CCRT耐药肿瘤细胞驱动。机械上,ACKR2表达响应于CCRT而增加,并且还通过由活化的髓样细胞和T细胞产生的CC趋化因子的连接而上调。随后，ACKR2+肿瘤细胞诱导产生转化生长因子β驱动CD8+T细胞衰老,从而损害抗肿瘤免疫力。此外，回顾性分析显示，在CCRT后复发的宫颈癌患者中，ACKR2表达和CD8+T细胞衰老增强，提示预后不良。总的来说,我们确定了驱动CD8+T细胞衰老和肿瘤复发的CCRT耐药ACKR2+肿瘤细胞亚群,并强调了ACKR2和CD8+T细胞衰老对放化疗复发的预后价值.
