Bcl6 controls the stability and suppressive function of regulatory T cells in head and neck squamous cell carcinoma

IF 6.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases Pub Date : 2024-12-26 DOI:10.1016/j.gendis.2024.101505

Shuqiong Wen , Xingxing Su , Junyi Guo , Zhanpeng Ou , Lisha Wang , Zhengliang Yue , Jing Zhao , Ling Ran , Jianjun Hu , Yuzhu Wang , Mengqu Ran , Qinyi He , Ping Ji , Lilin Ye , Zhiyu Chen , Lifan Xu , Qizhao Huang

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引用次数: 0

Abstract

Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most common cancer globally. Most studies in HNSCC demonstrated that regulatory T (Treg) cells confine the anti-tumor activity of effector T cells which may contribute to the immune escape and uncontrolled tumor progression. Here, we uncovered that the specific abrogation of Bcl6 in Treg cells resulted in significantly delayed malignant transformation of 4NQO-induced tumorigenesis. Bcl6 deficiency impairs the lineage stability of Treg cells by down-regulating the histone H3K4 trimethylation. Importantly, Bcl6 inhibition repressed the tumor growth of murine HNSCC and exhibited synergistic effects with immune checkpoint blockade therapy. These findings suggest that Bcl6 can be exploited as a promising therapeutic target for HNSCC treatment.

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Bcl6在头颈部鳞状细胞癌中控制调节性T细胞的稳定性和抑制功能

头颈部鳞状细胞癌（HNSCC）是全球第六大常见癌症。大多数HNSCC的研究表明，调节性T （Treg）细胞限制了效应T细胞的抗肿瘤活性，这可能有助于免疫逃逸和不受控制的肿瘤进展。在这里，我们发现Treg细胞中Bcl6的特异性缺失导致4nqo诱导的肿瘤发生的恶性转化显著延迟。Bcl6缺乏通过下调组蛋白H3K4三甲基化而损害Treg细胞的谱系稳定性。重要的是，Bcl6抑制抑制了小鼠HNSCC的肿瘤生长，并与免疫检查点阻断疗法表现出协同作用。这些发现表明Bcl6可以作为HNSCC治疗的一个有希望的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Genes & Diseases Multiple-

CiteScore

7.30

自引率

0.00%

发文量

347

审稿时长

49 days

期刊介绍： Genes & Diseases is an international journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch. Aims and Scopes Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis will be placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.