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

Zhuoyang Fan; Zhuoyang Fan; Zhuoyang Fan; Guowei Yang; Guowei Yang; Rongkui Luo; Xudong Qu; Xudong Qu; Xudong Qu; Xiaodan Ye; Jianhua Wang; Jianhua Wang; Jianhua Wang; Zhiping Yan; Zhiping Yan; Zhiping Yan; Minfeng Shu; Wei Zhang; Wei Zhang; Wei Zhang; Rong Liu; Rong Liu; Rong Liu; Rong Liu

doi:10.3389/fimmu.2023.1290185

Frontiers in Immunology (Jan 2024)

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

Zhuoyang Fan,
Zhuoyang Fan,
Zhuoyang Fan,
Guowei Yang,
Guowei Yang,
Rongkui Luo,
Xudong Qu,
Xudong Qu,
Xudong Qu,
Xiaodan Ye,
Jianhua Wang,
Jianhua Wang,
Jianhua Wang,
Zhiping Yan,
Zhiping Yan,
Zhiping Yan,
Minfeng Shu,
Wei Zhang,
Wei Zhang,
Wei Zhang,
Rong Liu,
Rong Liu,
Rong Liu,
Rong Liu

Affiliations

Zhuoyang Fan: Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
Zhuoyang Fan: Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
Zhuoyang Fan: National Clinical Research Center for Interventional Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
Guowei Yang: Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
Guowei Yang: National Clinical Research Center for Interventional Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
Rongkui Luo: Department of Pathology, Zhongshan Hospital of Fudan University, Shanghai, China
Xudong Qu: Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
Xudong Qu: Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
Xudong Qu: National Clinical Research Center for Interventional Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
Xiaodan Ye: Department of Radiology, Zhongshan Hospital of Fudan University, Shanghai, China
Jianhua Wang: Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
Jianhua Wang: Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
Jianhua Wang: National Clinical Research Center for Interventional Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
Zhiping Yan: Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
Zhiping Yan: Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
Zhiping Yan: National Clinical Research Center for Interventional Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
Minfeng Shu: Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
Wei Zhang: Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
Wei Zhang: Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
Wei Zhang: National Clinical Research Center for Interventional Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
Rong Liu: Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
Rong Liu: Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
Rong Liu: National Clinical Research Center for Interventional Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
Rong Liu: Department of Interventional Radiology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China

DOI: https://doi.org/10.3389/fimmu.2023.1290185
Journal volume & issue: Vol. 14

Abstract

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IntroductionHeat 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.MethodsWe 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.ResultsNotably, 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 the presence of lactic acid.DiscussionCollectively, these findings illuminate the intertwined mechanisms of sublethal heat treatments, metabolic alterations, and immune modulation in the tumor milieu, providing a deeper understanding of the complex interplay in cancer biology and treatment.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

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