A novel peptide targeting CCR7 inhibits tumor cell lymph node metastasis

• DOI: 10.1007/s00262-025-03995-4
• Publication Date: 2025-03-19T14:30:33Z
• Authors: Yixuan Sun; Yuzhen Qian; Lu Qiu; Xueqin Zhu; Haoming Ning; Liwei Pang; Xiaoshuang Niu; Yi Liu; Xiuman Zhou; Guanyu Chen; Wenjie Zhai; Yanfeng Gao

Lymph nodes are the most common metastasis sites for tumor cells, which intimately linked to patient prognosis. It has been reported that cancer cells can upregulate CC Chemokine Receptor 7 (CCR7) expression and hijack its normal functions, enabling them migrate along gradient of CCL19 CCL21 toward lymph colonies as initial stage distant metastasis. In patients, metastatic in exhibited higher CCR7, well inhibitory immune checkpoints PD-1, LAG-3, TIM-3 compared primary tumors with analysis TCGA GEO databases. Also, mouse model, elevated CCR7 were more susceptible develop popliteal node Subsequently, we successfully identified a binding peptide TC6 by phage display biopanning, specifically blocks interaction CCR7/CCL19 CCR7/CCL21. Further, D-amino acids introduced substitute N- C-terminus obtain proteolysis-resistant TC6-D3 peptide, decreased cell migration vitro via ERK1/2 pathway inhibited growth vivo, effectively restored T cytotoxicity both nodes. conclusion, promoted anti-tumor responses Specific blockade significantly reduce burden, promoting CD8+ infiltration tumors, meanwhile, enhancing