Tumor Cells Hijack Coagulation Signaling to Enable Immune Escape and Metastatic Dissemination
Year: 2026
Type: article
Abstract: Lymph node metastasis (LNM) represents a pivotal event in cancer progression and a major determinant of response to immune checkpoint blockade (ICB). Elucidation of the molecular mechanisms linking metastatic dissemination to immune suppression could identify potential therapeutic targets to improve ICB efficacy. Here, we identified the coagulation initiator tissue factor (F3) as a central regulator bridging tumor metastasis and immune evasion in gastric cancer (GC). F3 was significantly upregulated in LNM-positive tumors and correlated with impaired ICB responsiveness and poor clinical outcome. Mechanistically, the intracellular domain of F3 directly bound eEF1A1 to promote STAT3 phosphorylation and induce CCL20 expression, which selectively recruited CCR6+ regulatory T cells (Tregs) to establish an immunosuppressive microenvironment. Disruption of this F3–eEF1A1–STAT3–CCL20 axis with the clinically approved compound olsalazine disodium served as a compelling preclinical proof-of-concept to potently suppress tumor growth, abrogate Treg infiltration, and restore ICB sensitivity, all without perturbing basal coagulation. These findings redefine F3 from a canonical coagulation initiator to a tumor-intrinsic immunomodulator and reveal a druggable vulnerability that uncouples its oncogenic signaling from hemostasis.
Source: Cancer Research
Authors: Shuang Wang, Jiliang Lin, Zhou-Kai Zhao, Baishen Zhang, NianDong Yi, Xin-ke Zhang, Fei-Yang Zhang, Yongqiang Zheng, Xiao-Jiang Chen, Guo-Ming Chen, Zi-Qi Zheng, Tao Zhang, Chengcai Liang, Bai-Wei Zhao, Xiao-Xia Cai, Jin-Ling Duan, Xueyi Zheng, Chunhua Qu, Jierong Chen, Zhiwei Zhou, Ying-Bo Chen, Shuqiang Yuan, Sachiyo Nomura, Yuan-Fang Li, Run-Cong Nie, MuYan Cai
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7225609358
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