组蛋白修饰在弥漫大B细胞淋巴瘤中调控免疫细胞功能的作用

doi:10.16352/j.issn.1001-6325.2026.05.0711

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (5): 711-716.doi: 10.16352/j.issn.1001-6325.2026.05.0711

组蛋白修饰在弥漫大B细胞淋巴瘤中调控免疫细胞功能的作用

焦利超, 朱玉冰, 王灿灿, 冯宁, 李新霞^*

新疆医科大学第三临床医学院病理科,新疆乌鲁木齐 830011

收稿日期:2025-08-29 修回日期:2025-12-30 出版日期:2026-05-05 发布日期:2026-04-28
通讯作者: ^*lxx-patho@163.com
基金资助:
国家自然科学基金(82360037)

Role of histone modifications in regulating immune cell function in diffuse large B-cell lymphoma

JIAO Lichao, ZHU Yubing, WANG Cancan, FENG Ning, LI Xinxia^*

Department of Pathology, the Third Affiliated Clinical College of Xinjiang Medical University, Urumqi 830011, China

Received:2025-08-29 Revised:2025-12-30 Online:2026-05-05 Published:2026-04-28
Contact: ^*lxx-patho@163.com

摘要/Abstract

摘要： 弥漫大B细胞淋巴瘤(DLBCL)发病机制复杂,具有显著异质性。在DLBCL中,组蛋白修饰作为表观遗传调控的核心机制,其依赖于关键修饰酶的动态调节。KMT2D、EZH2、CREBBP和EP300等关键修饰酶的突变或失活,导致H3K4、H3K18和H3K27位点修饰异常,介导下游基因的异常激活或抑制,最终影响MYC、TP53和BCL6等蛋白的表达,促进细胞的增殖与恶性转化。同时,组蛋白修饰通过介导FBXW7/NOTCH/MYC/TGF-β1以及FBXW7/NOTCH/CCL2/CSF1等信号转导通路促进肿瘤相关巨噬细胞(TAMs)极化、抑制T细胞活化与杀伤功能,破坏抗肿瘤免疫稳态,促进DLBCL细胞免疫逃逸。

关键词: 弥漫大B细胞淋巴瘤, 组蛋白修饰, 免疫细胞

Abstract: Diffuse large B-cell lymphoma (DLBCL) exhibits complex pathogenesis and significant heterogeneity. In DLBCL, histone modifications serve as a core mechanism of epigenetic regulation, dependent on the dynamic regulation of key modifying enzymes. Mutations or inactivation of key modifying enzymes such as KMT2D, EZH2, CREBBP, and EP300 lead to abnormal modifications at H3K4, H3K18, and H3K27 sites. These alterations mediate abnormal activation or suppression of downstream genes, ultimately affecting the expression of proteins like MYC, TP53 and BCL6 to promote cell proliferation and malignant transformation. Concurrently, histone modifications promote tumor-associated macrophages(TAMs) polarization by mediating signaling pathways like FBXW7/NOTCH/MYC/TGF-β1 and FBXW7/NOTCH/CCL2/CSF1. This suppresses T-cell activation and killing functions, disrupts anti-tumor immune homeostasis, and facilitates immune escape in DLBCL cells.

Key words: diffuse large B-cell lymphoma(DLBCL), histone modifications, immune cell

中图分类号:

R733.4

焦利超, 朱玉冰, 王灿灿, 冯宁, 李新霞. 组蛋白修饰在弥漫大B细胞淋巴瘤中调控免疫细胞功能的作用[J]. 基础医学与临床, 2026, 46(5): 711-716.

JIAO Lichao, ZHU Yubing, WANG Cancan, FENG Ning, LI Xinxia. Role of histone modifications in regulating immune cell function in diffuse large B-cell lymphoma[J]. Basic & Clinical Medicine, 2026, 46(5): 711-716.

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组蛋白修饰在弥漫大B细胞淋巴瘤中调控免疫细胞功能的作用

Role of histone modifications in regulating immune cell function in diffuse large B-cell lymphoma

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