Peng Xiaopei, He Zhenhu, Yuan Dandan, Liu Zhenguo, Rong Pengfei
Department of Radiology, the Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Molecular Imaging Research Center, Central South University, Changsha, Hunan 410013, China.
Department of Infectious Disease, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
Biochim Biophys Acta Rev Cancer. 2024 Sep;1879(5):189164. doi: 10.1016/j.bbcan.2024.189164. Epub 2024 Aug 2.
As a solid tumor with high glycolytic activity, hepatocellular carcinoma (HCC) produces excess lactic acid and increases extracellular acidity, thus forming a unique immunosuppressive microenvironment. L-lactate dehydrogenase (LDH) and monocarboxylate transporters (MCTs) play a very important role in glycolysis. LDH is the key enzyme for lactic acid (LA) production, and MCT is responsible for the cellular import and export of LA. The synergistic effect of the two promotes the formation of an extracellular acidic microenvironment. In the acidic microenvironment of HCC, LA can not only promote the proliferation, survival, transport and angiogenesis of tumor cells but also have a strong impact on immune cells, ultimately leading to an inhibitory immune microenvironment. This article reviews the role of LA in HCC, especially its effect on immune cells, summarizes the progress of LDH and MCT-related drugs, and highlights the potential of immunotherapy targeting lactate combined with HCC.
作为一种具有高糖酵解活性的实体瘤，肝细胞癌（HCC）产生过量乳酸并增加细胞外酸度，从而形成独特的免疫抑制微环境。L-乳酸脱氢酶（LDH）和单羧酸转运体（MCTs）在糖酵解中起非常重要的作用。LDH是乳酸（LA）产生的关键酶，而MCT负责LA的细胞内外转运。两者的协同作用促进细胞外酸性微环境的形成。在HCC的酸性微环境中，LA不仅可以促进肿瘤细胞的增殖、存活、迁移和血管生成，还对免疫细胞有强烈影响，最终导致免疫抑制微环境。本文综述了LA在HCC中的作用，尤其是其对免疫细胞的影响，总结了LDH和MCT相关药物的研究进展，并强调了针对乳酸的免疫疗法联合HCC治疗的潜力。
