综合单细胞转录组分析揭示间变性甲状腺癌的免疫抑制景观
Integrative single-cell transcriptome analysis reveals immune suppressive landscape in the anaplastic thyroid cancer
原文发布日期:2023-09-07
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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.
ATC的肿瘤免疫微环境(TIME)是一个复杂多样的生态系统,全面了解该环境对于改善癌症治疗和预后至关重要。然而,ATC与PTC的肿瘤免疫微环境及其动态变化尚未在单细胞层面得到揭示。本研究对PTC和ATC原发肿瘤样本进行了整合性单细胞分析,发现免疫抑制细胞和分子在ATC的TIME中占主导地位。具体表现为:耗竭性CD8+ T细胞和M2巨噬细胞浸润水平升高,而NK细胞、B细胞和M1巨噬细胞浸润水平降低;CD8+ T细胞、γδT细胞和NK细胞的细胞毒性作用减弱;且LAG3、PD1、HAVCR2、TIGIT等免疫检查点分子在ATC中高表达。这些发现有助于深化对PTC和ATC肿瘤免疫微环境的理解,并揭示ATC特异性免疫抑制因素,针对这些免疫抑制因素进行干预可能激活ATC的抗肿瘤免疫应答。
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