失调的乳酸脱氢酶A在免疫细胞内抗肿瘤免疫中的调控作用
The regulatory roles of dysregulated lactate dehydrogenase A in anti-tumor immunity within immune cells.
摘要(中文译文)
恶性肿瘤通过代谢重编程维持其增殖、侵袭和转移能力。乳酸脱氢酶A（LDHA）是一种关键的糖酵解酶，在多种人类恶性肿瘤中异常高表达。LDHA的酶活性受到多种翻译后修饰的严密调控，包括乙酰化、磷酸化和乳酸化。LDHA促进Warburg效应和乳酸积累，同时参与肿瘤DNA损伤修复、恶性进展和耐药。LDHA及其代谢产物乳酸显著调节肿瘤浸润免疫细胞（包括淋巴样细胞和髓样细胞）的分化和功能状态。这些代谢变化重塑肿瘤免疫微环境，并以环境依赖的方式调控抗肿瘤免疫应答。本综述系统总结了LDHA在免疫细胞代谢和抗肿瘤免疫中的调控机制。此外，还讨论了LDHA作为一种有前景的抗肿瘤治疗靶点的临床潜力，并探讨了LDHA抑制剂与免疫疗法（如嵌合抗原受体T细胞（CAR-T）疗法和免疫检查点阻断）联合应用的前景。本研究旨在为肿瘤靶向治疗的研究与开发提供新视角。
Abstract
Malignant tumors maintain proliferative, invasive, and metastatic capacities through metabolic reprogramming. Lactate dehydrogenase A (LDHA), is an essential glycolytic enzyme that is aberrantly overexpressed in diverse human malignancies. The enzymatic activity of LDHA is tightly modulated by multiple post-translational modifications, including acetylation, phosphorylation, and lactylation. LDHA promotes the Warburg effect and lactate accumulation, while participating in tumor DNA damage repair, malignant progression, and drug resistance. LDHA and its metabolite lactate substantially modulate the differentiation and functional status of tumor-infiltrating immune cells, including lymphoid and myeloid cells. These metabolic changes remodel the tumor immune microenvironment and regulate anti-tumor immune responses in a context-dependent manner. This review systematically summarizes the regulatory mechanisms of LDHA in immune cell metabolism and anti-tumor immunity. Additionally, it discusses the clinical potential of LDHA as a promising anti-tumor therapeutic target and explores the application prospects of combining LDHA inhibitors with immunotherapies, such as chimeric antigen receptor T-cell (CAR-T) therapy and immune checkpoint blockade. This study aims to provide novel perspectives for the research and development of tumor targeted therapies.
如何引用
AMA
Xiaole Song, Shitong Lin, Qianwen Liu, Xuerou Chen, Yajuan Ma, Xiaoran Zhang, et al. The regulatory roles of dysregulated lactate dehydrogenase A in anti-tumor immunity within immune cells.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1847542.
APA
Xiaole Song, Shitong Lin, Qianwen Liu, Xuerou Chen, Yajuan Ma, Xiaoran Zhang, et al (2026). The regulatory roles of dysregulated lactate dehydrogenase A in anti-tumor immunity within immune cells.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1847542
GB/T 7714
Xiaole Song, Shitong Lin, Qianwen Liu, Xuerou Chen, Yajuan Ma, Xiaoran Zhang, et al. The regulatory roles of dysregulated lactate dehydrogenase A in anti-tumor immunity within immune cells.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1847542.
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