调节性 T 细胞:免疫浸润肿瘤微环境的障碍。

Regulatory T Cells: Barriers of Immune Infiltration Into the Tumor Microenvironment.

机构信息

Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.

Tumor Microenvironment Center, University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, Pittsburgh, PA, United States.

出版信息

Front Immunol. 2021 Jun 10;12:702726. doi: 10.3389/fimmu.2021.702726. eCollection 2021.

Abstract

Regulatory T cells (T) are key immunosuppressive cells that promote tumor growth by hindering the effector immune response. T utilize multiple suppressive mechanisms to inhibit pro-inflammatory responses within the tumor microenvironment (TME) by inhibition of effector function and immune cell migration, secretion of inhibitory cytokines, metabolic disruption and promotion of metastasis. In turn, T are being targeted in the clinic either alone or in combination with other immunotherapies, in efforts to overcome the immunosuppressive TME and increase anti-tumor effects. However, it is now appreciated that T not only suppress cells intratumorally direct engagement, but also serve as key interactors in the peritumor, stroma, vasculature and lymphatics to limit anti-tumor immune responses prior to tumor infiltration. We will review the suppressive mechanisms that T utilize to alter immune and non-immune cells outside and within the TME and discuss how these mechanisms collectively allow T to create and promote a physical and biological barrier, resulting in an immune-excluded or limited tumor microenvironment.

摘要

调节性 T 细胞(T 细胞)是关键的免疫抑制细胞,通过抑制效应免疫反应促进肿瘤生长。T 细胞利用多种抑制机制,通过抑制效应功能和免疫细胞迁移、分泌抑制性细胞因子、代谢紊乱和促进转移,来抑制肿瘤微环境(TME)中的促炎反应。反过来,T 细胞在临床上被单独或与其他免疫疗法联合靶向治疗,以克服免疫抑制的 TME 并增强抗肿瘤作用。然而,现在人们已经认识到,T 细胞不仅抑制肿瘤内的细胞直接接触,而且作为肿瘤周围、基质、血管和淋巴管中的关键相互作用者,在肿瘤浸润之前限制抗肿瘤免疫反应。我们将回顾 T 细胞利用来改变 TME 内外免疫和非免疫细胞的抑制机制,并讨论这些机制如何共同使 T 细胞形成并促进物理和生物屏障,导致免疫排斥或有限的肿瘤微环境。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61e9/8222776/e5fa68480e4d/fimmu-12-702726-g001.jpg

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