Sublethal heat treatment enhances lactic acid uptake in macrophages via MCT1, leading to reduced paraspeckle formation and a subsequent decrease in macrophage pyroptosis

作者：Zhuoyang Fan, Guowei Yang, Rongkui Luo, Xu-Dong Qu, Xiaodan Ye, Jianhua Wang, Zhiping Yan, Minfeng Shu, Wei Zhang, Rong Liu · 发表于：Frontiers in Immunology · 年份：2024 · DOI：10.3389/fimmu.2023.1290185 · 被引用次数：5 · 研究领域：Cancer, Hypoxia, and Metabolism、Immune cells in cancer、Ferroptosis and cancer prognosis

Introduction: Heat ablation is one of the key modalities in treating liver cancer, yet the residual cancer tissues suffering sublethal heat treatment possess a potential for increased malignancy. This study conducts a comprehensive analysis of cellular dynamics, metabolic shifts, and macrophage polarization within the tumor microenvironment following sublethal heat treatment. Methods: We observed significant acidification in tumor cell supernatants, attributed to increased lactic acid production. The study focused on how this pH shift, crucial in tumor progression and resistance, influences macrophage polarization, especially towards the M2 phenotype known for tumor-promoting functions. We also examined the upregulation of MCT1 expression post sublethal heat treatment and its primary role in lactic acid transport. Results: Notably, the study found minimal disparity in MCT1 expression between hepatocellular carcinoma patients and healthy liver tissues, highlighting the complexity of cancer biology. The research further revealed an intricate relationship between lactic acid, MCT1, and the inhibition of macrophage pyroptosis, offering significant insights for therapeutic strategies targeting the tumor immune environment. Post sublethal heat treatment, a reduction in paraspeckle under lactic acid exposure was observed, indicating diverse cellular impacts. Additionally, PKM2 was identified as a key molecule in this context, with decreased levels after sublethal heat treatment in t...