Bcl6 Preserves the Suppressive Function of Regulatory T Cells During Tumorigenesis
Bcl6 Preserves the Suppressive Function of Regulatory T Cells During Tumorigenesis
复制标题
Bcl6 在肿瘤发生过程中保留调节性 T 细胞的抑制功能
DOI：
10.3389/fimmu.2020.00806
复制
发表时间：
2020-05-12
影响因子：
7.3
通讯作者：
Xu, Lifan
中科院分区：
文献类型：
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作者：
Li, Yiding;Wang, Zhiming;Xu, Lifan
在肿瘤发生过程中，肿瘤浸润调节性T（Treg）细胞会限制肿瘤微环境中效应T细胞的功能，从而促进肿瘤生长。效应T细胞的抗肿瘤活性可通过治疗手段释放出来，目前正被用于治疗各类人类癌症。然而，Treg细胞的免疫抑制功能仍是肿瘤免疫治疗更广泛发挥疗效的主要障碍。在本文中，我们报道了特异性敲除Treg细胞中的Bcl6会导致肿瘤生长受阻，这是由Treg细胞反应受损所致。值得注意的是，Bcl6对于维持肿瘤微环境中Treg细胞的谱系稳定性至关重要。同时，我们发现，Foxp3（+）细胞中Bcl6缺失导致滤泡调节性T（Tfr）细胞缺失，而这对肿瘤控制并非必需。重要的是，Treg细胞中Bcl6表达增加与人类结直肠癌预后不良以及皮肤黑色素瘤的淋巴结转移相关。此外，Treg细胞中Bcl6缺失与免疫检查点阻断疗法具有协同效应。综上所述，这些结果表明，Bcl6在肿瘤发生过程中积极参与调节Treg细胞免疫反应，可作为抗肿瘤免疫的一个治疗靶点。
During tumorigenesis, tumor infiltrating regulatory T (Treg) cells restrict the function of effector T cells in tumor microenvironment and thereby promoting tumor growth. The anti-tumor activity of effector T cells can be therapeutically unleashed, and is now being exploited for the treatment of various types of human cancer. However, the immune suppressive function of Treg cells remains a major hurdle to broader effectiveness of tumor immunotherapy. In this article, we reported that the deletion of Bcl6 specifically in Treg cells led to stunted tumor growth, which was caused by impaired Treg cell responses. Notably, Bcl6 is essential in maintaining the lineage stability of Treg cells in tumor microenvironment. Meanwhile, we found that the absence of follicular regulatory T (Tfr) cells, which is a result of Bcl6 deletion in Treg cells, was dispensable for tumor control. Importantly, the increased Bcl6 expression in Treg cells is associated with poor prognosis of human colorectal cancer. Furthermore, Bcl6 deletion in Treg cells exhibits synergistic effects with immune checkpoint blockade therapy. Collectively, these results indicate that Bcl6 actively participates in regulating Treg cell immune responses during tumorigenesis and can be exploited as a therapeutic target of anti-tumor immunity.