Emerging involvement of CXCL13 in cancer development and progression

CXCL13, a chemokine originally identified for its role in B-cell trafficking, signals through the G-protein-coupled receptor CXCR5, to organize germinal centers and maintain immune architecture in secondary lymphoid organs. Beyond its physiological functions, accumulating evidence implicates the CXCL13-CXCR5 axis in the reciprocal regulation of inflammation and cancer. In this review, we outline our current understanding of its molecular organization, signaling properties, and regulatory feedback loops that fine-tune receptor activity. We further examine how CXCL13-CXCR5 signaling contributes to aquisition of cancer hallmarks, mainly through angiogenesis, epithelial-mesenchymal transition, metastatic niche conditioning, and the formation of tertiary lymphoid structures that influence antitumor immunity. By integrating biochemical, structural, and immunological insights, this review highlights the CXCL13-CXCR5 axis as a critical interface between lymphoid neogenesis and tumor evolution, and as a potential target for therapeutic modulation in cancer.