CD2–CD58 axis orchestrates cytotoxic T lymphocyte function and metabolic crosstalk in breast cancer brain metastasis

IF 3.9 3区生物学 Q3 CELL BIOLOGY

Journal of Cell Communication and Signaling Pub Date : 2025-08-24 DOI:10.1002/ccs3.70040

Guanyou Huang, Yigong Wei, Xiaohong Hou, Xin Jia, Yong Yu, Xu Li, Shanshan Yu

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Abstract

This study investigates the impact of the CD2–CD58 signaling axis on effector T cell function and tumor metabolic crosstalk in breast cancer brain metastasis (BCBM) using single-cell transcriptomic analysis. scRNA-seq data analysis revealed the critical role of CD2–CD58 signaling between CD8⁺ T cells and tumor cells in BCBM. Functional assays demonstrated that CD2 knockdown inhibited cytotoxic T lymphocyte (CTL) proliferation, activation, and cytotoxicity, leading to impaired tumor cell recognition and enhanced proliferation, migration, and invasion. In vivo studies showed that CD2-deficient CTLs promoted tumor growth and brain metastasis while affecting metabolic reprogramming by altering key enzyme expressions in pyrimidine biosynthesis and arginine metabolism pathways. The findings suggest that CD2 enhances CTL function against tumor cells and influences their metabolic states, highlighting the role of CD2 in remodeling the brain metastatic microenvironment in breast cancer.

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CD2-CD58轴在乳腺癌脑转移中协调细胞毒性T淋巴细胞功能和代谢串扰

本研究利用单细胞转录组学分析研究了CD2-CD58信号轴对乳腺癌脑转移（BCBM）中效应T细胞功能和肿瘤代谢串音的影响。scRNA-seq数据分析揭示了CD2-CD58信号在BCBM中CD8+ T细胞和肿瘤细胞之间的关键作用。功能分析表明，CD2敲低抑制细胞毒性T淋巴细胞（CTL）的增殖、激活和细胞毒性，导致肿瘤细胞识别受损，增殖、迁移和侵袭增强。体内研究表明，缺乏cd2的ctl促进肿瘤生长和脑转移，同时通过改变嘧啶生物合成和精氨酸代谢途径中关键酶的表达影响代谢重编程。研究结果表明，CD2增强了CTL对肿瘤细胞的功能，并影响其代谢状态，突出了CD2在乳腺癌脑转移微环境重塑中的作用。

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来源期刊

Journal of Cell Communication and Signaling CELL BIOLOGY-

CiteScore

6.40

自引率

4.90%

发文量

期刊介绍： The Journal of Cell Communication and Signaling provides a forum for fundamental and translational research. In particular, it publishes papers discussing intercellular and intracellular signaling pathways that are particularly important to understand how cells interact with each other and with the surrounding environment, and how cellular behavior contributes to pathological states. JCCS encourages the submission of research manuscripts, timely reviews and short commentaries discussing recent publications, key developments and controversies. Research manuscripts can be published under two different sections : In the Pathology and Translational Research Section (Section Editor Andrew Leask) , manuscripts report original research dealing with celllular aspects of normal and pathological signaling and communication, with a particular interest in translational research. In the Molecular Signaling Section (Section Editor Satoshi Kubota) manuscripts report original signaling research performed at molecular levels with a particular interest in the functions of intracellular and membrane components involved in cell signaling.