Data from Breast Cancer Stem Cells Secrete MIF to Mediate Tumor Metabolic Reprogramming That Drives Immune Evasion

• DOI: 10.1158/0008-5472.c.7181269.v1
• Publication Date: 2024-04-15T07:20:42Z
• Authors: Linlin Yan; Mingming Wu; Tianyu Wang; Hui Yuan; Xiao Zhang; Huafeng Zhang; Tao Li; Vijay Pandey; Xinghua Han; Peter E. Lobie; Tao Zhu
• Keywords: Triple-negative breast cancer; Reprogramming

<div>Abstract<p>Reprogramming of energy metabolism exerts pivotal functions in cancer progression and immune surveillance. Identification the mechanisms mediating metabolic changes may lead to improved strategies suppress tumor growth stimulate antitumor immunity. Here, it was observed that secretomes hypoxic breast cells stem (BCSC) induced reprogramming pathways, particularly glycolysis, normoxic cells. Screening BCSC secretome identified MIF as a factor potentiating glycolysis. Mechanistically, increased c-MYC–mediated transcriptional upregulation glycolytic enzyme aldolase C by activating WNT/β-catenin signaling. Targeting attenuated glycolysis impaired xenograft metastasis. depletion also augmented intratumoral cytolytic CD8<sup>+</sup> T proinflammatory macrophages while decreasing regulatory tumor-associated neutrophils microenvironment. Consequently, targeting therapeutic efficacy checkpoint blockade triple-negative cancer. Collectively, this study proposes an attractive target circumvent immunosuppression cancer.</p>Significance:<p>MIF secreted induces bulk engenders immunosuppressive microenvironment, identifying strategy improve immunotherapy cancer.</p></div>