Targeting the Vim-PGIPathway Enhances CD8T Cell-Mediated Antitumor Immunity in Breast Cancer.

Abstract

Breast cancer is the most prevalent malignancy in women, and the limited effectiveness of current treatments highlights the need for novel immune regulatory mechanisms to improve long-term survival. This study investigated the role of Vim in PGIsynthesis and its impact on tumor immune regulation. Multiomics profiling revealed molecular alterations following Vim deletion, which were validated in murine breast cancer models using RT-qPCR, Western blot, ELISA, and flow cytometry, with rescue experiments involving exogenous PGI. The findings showed that Vim deletion downregulated arachidonic acid metabolism, reduced PTGIS expression, and significantly lowered PGIlevels. Functional assays demonstrated that Vim deficiency enhanced T cell-mediated antitumor immunity, evidenced by an increased proportion of CD8T cells, upregulation of cytotoxic genes (,,, and), and activation of inflammation-related signaling pathways, as indicated by enhanced phosphorylation of ERK1/2 and p65. Both exogenous PGIsupplementation and ozagrel treatment reversed these effects. In conclusion, the Vim-PGIaxis is identified as a key regulator of CD8T cell immunity in breast cancer, representing a potential therapeutic target and a critical consideration in anticoagulant management during cancer immunotherapy.