Single-cell dissection of cervical cancer reveals key subsets of the tumor immune microenvironment
Single-cell dissection of cervical cancer reveals key subsets of the tumor immune microenvironment
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宫颈癌的单细胞解析揭示了肿瘤免疫微环境的关键细胞亚群
DOI：
10.15252/embj.2022110757
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发表时间：
2023-07-10
期刊：
影响因子：
11.4
通讯作者：
Li, Fang
中科院分区：
文献类型：
--
作者：
Cao, Guangxu;Yue, Jiali;Li, Fang
肿瘤微环境(TME)直接决定患者的预后和治疗效果。为了改善宫颈癌患者的预后，需要对TME有深入的了解。这项研究对6对肿瘤和邻近的正常组织进行了单细胞RNA和TCR测序，以绘制CC免疫图景。T细胞和NK细胞在肿瘤区域高度浓缩，并从细胞毒性表型向耗竭表型转化。我们的分析表明，细胞毒性大克隆T细胞在抗肿瘤反应中是关键的效应者。这项研究还揭示了肿瘤特异性生发中心B细胞与三级淋巴结构相关。CC患者中高生发中心B细胞比例预示着临床结果的改善，并与激素免疫反应升高有关。我们描绘了免疫排斥的间质景观，并建立了肿瘤和间质细胞的联合模型来预测CC患者的预后。这项研究揭示了肿瘤生态系统亚群与TME的抗肿瘤反应或预后有关，并为未来的联合免疫治疗提供了信息。
The tumor microenvironment (TME) directly determines patients' outcomes and therapeutic efficiencies. An in-depth understanding of the TME is required to improve the prognosis of patients with cervical cancer (CC). This study conducted single-cell RNA and TCR sequencing of six-paired tumors and adjacent normal tissues to map the CC immune landscape. T and NK cells were highly enriched in the tumor area and transitioned from cytotoxic to exhaustion phenotypes. Our analyses suggest that cytotoxic large-clone T cells are critical effectors in the antitumor response. This study also revealed tumor-specific germinal center B cells associated with tertiary lymphoid structures. A high-germinal center B cell proportion in patients with CC is predictive of improved clinical outcomes and is associated with elevated hormonal immune responses. We depicted an immune-excluded stromal landscape and established a joint model of tumor and stromal cells to predict CC patients' prognosis. The study revealed tumor ecosystem subsets linked to antitumor response or prognosis in the TME and provides information for future combinational immunotherapy.