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肿瘤相关小胶质细胞/巨噬细胞与 CD8 阳性 T 细胞的串扰在胶质母细胞瘤中起关键作用。

Crosstalk Between Tumor-Associated Microglia/Macrophages and CD8-Positive T Cells Plays a Key Role in Glioblastoma.

机构信息

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

出版信息

Front Immunol. 2021 Jul 29;12:650105. doi: 10.3389/fimmu.2021.650105. eCollection 2021.

Abstract

Glioblastoma is considered to be the most malignant disease of the central nervous system, and it is often associated with poor survival. The immune microenvironment plays a key role in the development and treatment of glioblastoma. Among the different types of immune cells, tumor-associated microglia/macrophages (TAM/Ms) and CD8-positive (CD8+) T cells are the predominant immune cells, as well as the most active ones. Current studies have suggested that interaction between TAM/Ms and CD8+ T cells have numerous potential targets that will allow them to overcome malignancy in glioblastoma. In this review, we summarize the mechanism and function of TAM/Ms and CD8+ T cells involved in glioblastoma, as well as update on the relationship and crosstalk between these two cell types, to determine whether this association alters the immune status during glioblastoma development and affects optimal treatment. We focus on the molecular factors that are crucial to this interaction, and the role that this crosstalk plays in the biological processes underlying glioblastoma treatment, particularly with regard to immune therapy. We also discuss novel therapeutic targets that can aid in resolving reticular connections between TAM/Ms and CD8+ T cells, including depletion and reprogramming TAM/Ms and novel TAM/Ms-CD8+ T cell cofactors with potential translational usage. In addition, we highlight the challenges and discuss future perspectives of this crosstalk between TAM/Ms and CD8+ T cells.

摘要

胶质母细胞瘤被认为是中枢神经系统中最恶性的疾病,常伴有不良预后。免疫微环境在胶质母细胞瘤的发生和治疗中起着关键作用。在不同类型的免疫细胞中,肿瘤相关的小胶质细胞/巨噬细胞(TAM/Ms)和 CD8+(CD8+)T 细胞是主要的免疫细胞,也是最活跃的免疫细胞。目前的研究表明,TAM/Ms 和 CD8+T 细胞之间的相互作用有许多潜在的靶点,这些靶点将使它们能够克服胶质母细胞瘤的恶性程度。在这篇综述中,我们总结了 TAM/Ms 和 CD8+T 细胞在胶质母细胞瘤中涉及的机制和功能,以及更新了这两种细胞类型之间的关系和串扰,以确定这种关联是否改变了胶质母细胞瘤发展过程中的免疫状态并影响了最佳治疗效果。我们重点关注对这种相互作用至关重要的分子因素,以及这种串扰在胶质母细胞瘤治疗的生物学过程中所起的作用,特别是在免疫治疗方面。我们还讨论了一些新的治疗靶点,可以帮助解决 TAM/Ms 和 CD8+T 细胞之间的网状连接,包括耗尽和重编程 TAM/Ms 以及具有潜在转化用途的新型 TAM/Ms-CD8+T 细胞共因子。此外,我们强调了这种 TAM/Ms 和 CD8+T 细胞之间串扰的挑战,并讨论了未来的展望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c70/8358794/1caef8f536ce/fimmu-12-650105-g001.jpg

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