Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Wuhan University Shenzhen Research Institute, Shenzhen 518057, China.
Cancer Biol Med. 2024 Mar 25;21(6):513-40. doi: 10.20892/j.issn.2095-3941.2023.0382.
Abnormal metabolism is the underlying reason for breast cancer progression. Decreased lactate dehydrogenase B () has been detected in breast cancer but the function of remains unknown.
Western blot was used to analyze expression in breast cancer cells. The impact of on tumor cell migration and invasion was determined using Transwell assays, wound healing assays, and a mouse lung metastasis model. Subcutaneous tumor formation, a natural killer (NK) cell cytotoxicity assay, and flow cytometry evaluated NK cell activation. Immunofluorescence and quantitative real-time PCR detected NK cell activation markers. Kaplan-Meier analysis evaluated the effect of immune cell infiltration on prognosis. Single-sample gene set enrichment analysis determined NK cell activation scores. A support vector machine predicted the role of in NK cell activation.
In this study we showed that inhibits the breast cancer cell metastasis and orchestrates metabolic reprogramming within tumor cells. Our results revealed that -mediated lactic acid clearance in breast cancer cells triggers NK cell activation within the tumor microenvironment. Our findings, which were confirmed in a murine model, demonstrated that in tumor cells promotes NK cell activation and ultimately results in the eradication of malignant cells. Clinically, our study further validated that affects immune cell infiltration and function. Specifically, its expression has been linked to enhanced NK cell-mediated cytotoxicity and improved patient survival. Furthermore, we identified expression in tumors as an important predictor of NK cell activation, with strong predictive ability in some cancers.
Our results suggest that is a promising target for activating the tumor immune microenvironment in breast cancer, where -associated lactic acid clearance leads to increased NK cell activity. This study highlights the critical role of in regulating immune responses and its potential as a therapeutic target for breast cancer.
异常代谢是乳腺癌进展的根本原因。已经在乳腺癌中检测到乳酸脱氢酶 B () 的减少，但 的功能仍然未知。
使用 Western blot 分析乳腺癌细胞中的 表达。使用 Transwell 测定、划痕愈合测定和小鼠肺转移模型确定 对肿瘤细胞迁移和侵袭的影响。皮下肿瘤形成、自然杀伤 (NK) 细胞细胞毒性测定和流式细胞术评估 NK 细胞激活。免疫荧光和实时定量 PCR 检测 NK 细胞激活标志物。Kaplan-Meier 分析评估免疫细胞浸润对预后的影响。单样本基因集富集分析确定 NK 细胞激活评分。支持向量机预测 在 NK 细胞激活中的作用。
在这项研究中，我们表明 抑制乳腺癌细胞转移，并协调肿瘤细胞内的代谢重编程。我们的结果表明，-介导的乳腺癌细胞中乳酸清除触发肿瘤微环境中的 NK 细胞激活。我们的发现在小鼠模型中得到了证实，表明肿瘤细胞中的 促进 NK 细胞激活，最终导致恶性细胞的清除。临床上，我们的研究进一步验证了 影响免疫细胞浸润和功能。具体而言，其表达与增强的 NK 细胞介导的细胞毒性和改善患者生存相关。此外，我们确定了肿瘤中 的表达是 NK 细胞激活的重要预测因子，在某些癌症中具有很强的预测能力。
我们的研究结果表明， 在乳腺癌中是激活肿瘤免疫微环境的有前途的靶点，其中与乳酸清除相关的 导致 NK 细胞活性增加。这项研究强调了 在调节免疫反应中的关键作用及其作为乳腺癌治疗靶点的潜力。
