Transferrin Disassociates TCR from CD3 Signaling Apparatus to Promote Metastasis

	Transferrin Disassociates TCR from CD3 Signaling Apparatus to Promote Metastasis
	Cheng, RM; Tang, XP; Zhao, QY; Wang, YM; Chen, WL; Wang, G; Wang, CX; Mwangi, J; Lu, QM; Tadese, DA; Zhao, XD; Ou, CW; Lai, R
	2025
发表期刊	RESEARCH
ISSN	2096-5168
卷号	8
摘要	Immune recognition and activation by the peptide-laden major histocompatibility complex-T cell receptor (TCR)-CD3 complex is essential for anti-tumor immunity. Tumors may escape immune surveillance by dissembling the complex. Here, we report that transferrin, which is overexpressed in patients with liver metastasis, disassociates TCR from the CD3 signaling apparatus by targeting the constant domain (CD) of T cell receptor alpha (TCR alpha), consequently suppresses T cell activation, and inhibits anti-metastatic and anti-tumor immunity. In mouse models of melanoma and lymphoma, transferrin overexpression exacerbates liver metastasis, while its knockdown, antibody, designed peptides, and CD mutation interfering with transferrin-TCR alpha interaction inhibit metastasis. This work reveals a novel strategy of tumor evasion of immune surveillance by blocking the coupling between TCRs and the CD3 signaling apparatus to suppress TCR activation. Given the conservation of CD and transferrin up-regulation in metastatic tumors, the strategy might be a common metastatic mechanism. Targeting transferrin-TCR alpha holds promise for anti-metastatic treatment.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14532
专题	科研部门_天然药物功能蛋白质学科组（赖仞）
推荐引用方式 GB/T 7714	Cheng, RM,Tang, XP,Zhao, QY,et al. Transferrin Disassociates TCR from CD3 Signaling Apparatus to Promote Metastasis[J]. RESEARCH,2025,8.
APA	Cheng, RM.,Tang, XP.,Zhao, QY.,Wang, YM.,Chen, WL.,...&Lai, R.(2025).Transferrin Disassociates TCR from CD3 Signaling Apparatus to Promote Metastasis.RESEARCH,8.
MLA	Cheng, RM,et al."Transferrin Disassociates TCR from CD3 Signaling Apparatus to Promote Metastasis".RESEARCH 8(2025).

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