Liu Yansong, Hu Anbang, Shakila Suborna S, Cheng Weilun, Wang Ting, Zhang Jiarui, Yu Tianshui, Duan Yunqiang, Feng Jianyuan, Ding Yu, Zhang Hanyu, Li Yanling, Li Mingcui, Rong Zhiyuan, Shang Yuhang, Fang Zhengbo, Liu Jiangwei, Kong Fanjing, Guo Baoliang
Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Department of General Surgery, Daqing Oilfield General Hospital, Daqing 163316, China.
J Leukoc Biol. 2024 Dec 31;117(1). doi: 10.1093/jleuko/qiae190.
Hormone receptor-positive breast cancer (HR+ BRCA) with high-risk factors such as lymph node metastasis has a relatively poor prognosis. However, the biological basis of tumor cell migration is still poorly understood, especially as some of the metastatic events occur at an early stage. Here, we identified that CHST4 (carbohydrate sulfotransferase 4), which has an important role in lymphocyte homing, was abnormally downregulated in HR+ BRCA and associated with lymph node metastasis. By enrichment analysis and immune infiltration evaluation, we predicted the potential ability of CHST4 to enhance immune cell infiltration. Then, immunohistochemical staining further demonstrated the contribution of CHST4 to the infiltration abundance of CD8+ T cells and CD4+ T cells in HR+ BRCA. Immunohistochemical staining of MECA-79 further identified the correlation between CHST4 and sulfated peripheral node addressin. Finally, we demonstrated that CHST4 was connected to increased tumor-immune cell communication by analyzing single-cell sequencing data. In summary, our study provided novel insights into the regulation of HR+ BRCA immune infiltration by CHST4.
具有淋巴结转移等高风险因素的激素受体阳性乳腺癌(HR+ BRCA)预后相对较差。然而,肿瘤细胞迁移的生物学基础仍知之甚少,尤其是一些转移事件发生在早期阶段。在此,我们发现CHST4(碳水化合物硫酸转移酶4)在淋巴细胞归巢中起重要作用,在HR+ BRCA中异常下调,并与淋巴结转移相关。通过富集分析和免疫浸润评估,我们预测了CHST4增强免疫细胞浸润的潜在能力。然后,免疫组织化学染色进一步证明了CHST4对HR+ BRCA中CD8+ T细胞和CD4+ T细胞浸润丰度的贡献。MECA-79的免疫组织化学染色进一步确定了CHST4与硫酸化外周淋巴结地址素之间的相关性。最后,我们通过分析单细胞测序数据证明CHST4与增加的肿瘤-免疫细胞通讯有关。总之,我们的研究为CHST4对HR+ BRCA免疫浸润的调控提供了新的见解。