Targeting the Vim-PGI₂ Pathway Enhances CD8⁺ T Cell-Mediated Antitumor Immunity in Breast Cancer

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 PGI₂ synthesis 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 PGI₂. The findings showed that Vim deletion downregulated arachidonic acid metabolism, reduced PTGIS expression, and significantly lowered PGI₂ levels. Functional assays demonstrated that Vim deficiency enhanced T cell-mediated antitumor immunity, evidenced by an increased proportion of CD8⁺ T cells, upregulation of cytotoxic genes (Ifng, Gzmb, Tnf, and Klrd1), and activation of inflammation-related signaling pathways, as indicated by enhanced phosphorylation of ERK1/2 and p65. Both exogenous PGI₂ supplementation and ozagrel treatment reversed these effects. In conclusion, the Vim-PGI₂ axis is identified as a key regulator of CD8⁺ T cell immunity in breast cancer, representing a potential therapeutic target and a critical consideration in anticoagulant management during cancer immunotherapy.