综合单细胞转录组分析揭示了无形甲状腺癌中的免疫抑制景观。
Integrative single-cell transcriptome analysis reveals immune suppressive landscape in the anaplastic thyroid cancer.
发表日期:2023 Sep 07
作者:
Chao Feng, Yujia Tao, Chao Yu, Lirui Wang, Xiao Liu, Yuan Cao
来源:
CANCER GENE THERAPY
摘要:
甲状腺癌(ATC)的肿瘤免疫微环境(TIME)是一个复杂多样的生态系统。全面了解TIME以改善癌症治疗和预后至关重要。然而,目前尚未揭示PTC与ATC的TIME在单细胞水平上的动态变化。在本研究中,我们对PTC和ATC原发肿瘤样本进行了整合的单细胞分析。我们发现,免疫抑制性细胞和分子在ATC的TIME中占主导地位。具体而言,疲惫CD8+ T细胞和M2巨噬细胞的浸润水平增加,而NK细胞、B细胞和M1巨噬细胞的浸润水平降低。CD8+ T细胞、γδ T细胞和NK细胞的细胞毒性下降,免疫检查点分子如LAG3、PD1、HAVCR2和TIGIT在ATC中高表达。我们的研究结果有助于理解PTC和ATC中的TIME,为了解ATC特异性的免疫抑制因子提供了新的见解。针对这些免疫抑制因子可能激活ATC中的抗肿瘤免疫反应。© 2023. 版权所有 Springer Nature America, Inc. 未经独家许可。
The tumor immune microenvironment (TIME) in ATC is a complex and diverse ecosystem. It is essential to have a comprehensive understanding to improve cancer treatment and prognosis. However, TIME of ATC and the dynamic changes with PTC has not been revealed at the single-cell level. Here, we performed an integrative single-cell analysis of PTC and ATC primary tumor samples. We found that immunosuppressive cells and molecules dominated the TIME in ATC. Specifically, the level of infiltration of exhausted CD8+ T cells, and M2 macrophages was increased, and that of NK cells, B cells, and M1 macrophages was decreased. The cytotoxicity of CD8+ T cells, γδT cells, and NK cells was decreased, and immune checkpoint molecules, such as LAG3, PD1, HAVCR2, and TIGIT were highly expressed in ATC. Our findings contribute to the comprehension of TIME in both PTC and ATC, offering insights into the immunosuppressive factors specifically associated with ATC. Targeting these immunosuppressive factors may activate the anti-tumor immune response in ATC.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.