机构：[1]Key Laboratory of Genetic Evolution & Animal Models, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Sino-African Joint Research Center, and New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, Yunnan 650201, China.[2]Department of Clinical Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650108, China.[3]Third Department of Breast Surgery, Peking University Cancer Hospital Yunan, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, Yunnan 650118, China.[4]Division of Abdominal Tumor Multimodality Treatment and Laboratory of Animal Tumor Models, Cancer Center and State Key Laboratory of Respiratory Health and Multimorbidity and Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.四川大学华西医院[5]Department of Cardiology and Laboratory of Heart Center, Zhujiang Hospital, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Southern Medical University, Guangzhou, Guangdong 510515, China.南方医科大学珠江医院
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.
基金：
National Natural Science Foundation of China [31930015, U2002219, 32100907]; Chinese Academy of Sciences [KFJ-BRP-008-003, SAJC202402]; Yunnan Provincial Science and Technology Department [202003AD150008, 202202AA100002, 2023-01AT070344, 202305AH340007]; Kunming Science and Technology Bureau [2022SCP007]; New Cornerstone Investigator Program from Shenzhen New Cornerstone Science Foundation [NCI202238]; Yunnan Characteristic Plant Extraction Laboratory [2025YKZY002]; Tianfu Jincheng Laboratory Foundation [TFJC2023010007]; Yunnan Development and Reform Commission [202303]
第一作者机构：[1]Key Laboratory of Genetic Evolution & Animal Models, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Sino-African Joint Research Center, and New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, Yunnan 650201, China.
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推荐引用方式(GB/T 7714)：
Cheng Ruomei,Tang Xiaopeng,Zhao Qiyu,et al.Transferrin Disassociates TCR from CD3 Signaling Apparatus to Promote Metastasis[J].RESEARCH.2025,8:doi:10.34133/research.0578.
APA：
Cheng, Ruomei,Tang, Xiaopeng,Zhao, Qiyu,Wang, Yuming,Chen, Wenlin...&Lai, Ren.(2025).Transferrin Disassociates TCR from CD3 Signaling Apparatus to Promote Metastasis.RESEARCH,8,
MLA：
Cheng, Ruomei,et al."Transferrin Disassociates TCR from CD3 Signaling Apparatus to Promote Metastasis".RESEARCH 8.(2025)
