Hypoxia-driven remodeling of SELENOP+ macrophages shapes T cell dynamics and promotes ovarian cancer metastasis
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
TL;DR
This study explores how SELENOP+ macrophages in the tumor environment influence T cell activity and promote the spread of ovarian cancer.
Contribution
The study identifies SELENOP+ macrophages as key drivers of T cell dynamics and metastasis in ovarian cancer.
Findings
SELENOP+ macrophages activate CD8+ T cells via selenoprotein P in vitro and in vivo.
Anti-VEGFA intervention increases SELENOP+ macrophages and CD8+ T cell cytotoxicity in vivo.
Hypoxia-driven VEGFA-EPHB2 signaling promotes macrophage transitions and tumor metastasis.
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…
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Taxonomy
TopicsImmune cells in cancer · Ferroptosis and cancer prognosis · Cancer, Hypoxia, and Metabolism