AUTHOR=Liu Wenxi , Wu Jiaqi , Zhang Xinran , Zhang Yanhua , Zeng Xianqin , Peng Xiaochun 

TITLE=PKM2 orchestrates tumor progression via metabolic reprogramming and MDSCs-mediated immune suppression in the tumor microenvironment

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1588019

DOI=10.3389/fimmu.2025.1588019

ISSN=1664-3224

ABSTRACT=The tumor microenvironment (TME) is a complex system, in which the energy metabolism of tumor cells plays a key role in the occurrence, development and metastasis of tumors. In the TME, the energy supply of tumor cells mainly comes from glycolysis. This metabolic reprogramming phenomenon is usually called the Warburg effect. Despite the abundance of oxygen, tumor cells still preferentially utilize the glycolytic pathway to meet their bioenergetic demands. Pyruvate kinase (PK), as a key enzyme in glycolysis, plays an important role in the regulation of energy metabolism in tumor cells. Among them, pyruvate kinase M2 (PKM2) is highly expressed in tumors and promotes the release of cytokines by tumor cells, thereby recruiting myeloid-derived suppressor cells (MDSCs). These cytokines bind to the surface receptors of MDSCs, activate related signaling pathways, and up-regulate the expression of cathepsin cysteine proteases. This process subsequently inhibits the activity of T cells, thereby affecting tumor development.