Qing Liu, Chenzhao Feng, Tianhao Wu, Siyang Zhang, Xinyi Wang, Qian Zhao, Xueying Song, Shuangyan Liu, Linru Quan, Yuli Zhang, Shimin Zhang, Bin Yang, Jixin Li, Gang Chen, Xuanzhang Huang, Chaoyang Sun, Xin Zhou
Abstract High-grade serous ovarian cancer (HGSOC) is characterized by extensive transcoelomic dissemination and the accumulation of ascites. However, how site-specific tumor microenvironment (TME) drives progression remains unknown. Here we show the co-occurrence and spatial co-localization of SELENOP + macrophages and precursor exhausted CD8 + T cells and demonstrate that SELENOP + macrophages activate T cells via selenoprotein P in vitro and in vivo. We further identify a dynamic transition in the SELENOP + / SPP1 + macrophage populations as tumor metastasis, driven by increased hypoxia malignant epithelial cells through VEGFA-EPHB2 signaling. We also reveal that anti-VEGFA intervention controls ovarian tumor growth by increasing SELENOP + macrophages and cytotoxicity of CD8 + T cells in vivo. Taken together, these findings spotlight the role of tumor-induced TME remodeling in subverting immune-mediated tumor control and thus facilitating HGSOC metastasis in females. Collectively, our results provide a foundation for the development of targeted therapeutic interventions aimed at impeding HGSOC metastatic trajectory.