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肿瘤免疫抑制中的调节性 T 细胞——对癌症治疗的影响。

Regulatory T cells in cancer immunosuppression - implications for anticancer therapy.

机构信息

Division of Cancer Immunology, Research Institute/Exploratory Oncology Research and Clinical Trial Centre (EPOC), National Cancer Centre, Tokyo/Chiba, Japan.

Departments of Gastroenterology and Gastrointestinal Oncology, National Cancer Centre Hospital East, Kashiwa, Chiba, Japan.

出版信息

Nat Rev Clin Oncol. 2019 Jun;16(6):356-371. doi: 10.1038/s41571-019-0175-7.

Abstract

Regulatory T (T) cells, an immunosuppressive subset of CD4 T cells characterized by the expression of the master transcription factor forkhead box protein P3 (FOXP3), are a component of the immune system with essential roles in maintaining self-tolerance. In addition, T cells can suppress anticancer immunity, thereby hindering protective immunosurveillance of neoplasia and hampering effective antitumour immune responses in tumour-bearing hosts, thus promoting tumour development and progression. Identification of the factors that are specifically expressed in T cells and/or that influence T cell homeostasis and function is important to understanding cancer pathogenesis and to identifying therapeutic targets. Immune-checkpoint inhibitors (ICIs) have provided a paradigm shift in the treatment of cancer. Most immune-checkpoint molecules are expressed in T cells, but the effects of ICIs on T cells, and thus the contributions of these cells to treatment responses, remain unclear. Notably, evidence indicates that ICIs targeting programmed cell death 1 (PD-1) might enhance the immunosuppressive function of T cells, whereas cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors might deplete these cells. Thus, although manipulation of T cells is a promising anticancer therapeutic strategy, approaches to controlling these cells require further research. Herein, we discuss novel insights into the roles of T cells in cancer, which can hopefully be used to develop T cell-targeted therapies and facilitate immune precision medicine.

摘要

调节性 T(T)细胞是 CD4 T 细胞的一个免疫抑制亚群,其特征是表达主转录因子叉头框蛋白 P3(FOXP3),是免疫系统的一个组成部分,在维持自身耐受方面具有重要作用。此外,T 细胞可以抑制抗肿瘤免疫,从而阻碍肿瘤的保护性免疫监视,并阻碍荷瘤宿主中有效的抗肿瘤免疫反应,从而促进肿瘤的发展和进展。鉴定在 T 细胞中特异性表达的和/或影响 T 细胞稳态和功能的因子对于理解癌症发病机制和确定治疗靶点非常重要。免疫检查点抑制剂(ICIs)在癌症治疗方面带来了范式转变。大多数免疫检查点分子在 T 细胞中表达,但 ICI 对 T 细胞的影响,以及这些细胞对治疗反应的贡献仍不清楚。值得注意的是,有证据表明,针对程序性细胞死亡蛋白 1(PD-1)的 ICI 可能增强 T 细胞的免疫抑制功能,而细胞毒性 T 淋巴细胞相关抗原 4(CTLA-4)抑制剂可能耗尽这些细胞。因此,尽管操纵 T 细胞是一种很有前途的抗肿瘤治疗策略,但控制这些细胞的方法需要进一步研究。本文讨论了 T 细胞在癌症中的作用的新见解,希望这些见解能用于开发针对 T 细胞的治疗方法,并促进免疫精准医学的发展。

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