Ccl5, also known as RANTES (regulated on activation, normal T cell expressed and secreted), is a proinflammatory CC subfamily chemokine synthesized by T lymphocytes. It is involved in various biological processes such as immune regulation and cell migration. It participates in multiple pathways, and its dysregulation is associated with various diseases [3].

In pancreatic cancer, scRNA-seq analysis found CCL5-SDC1/4 receptor-ligand interactions between T cells and tumor cells, and CCL5 promoted tumor cell migration in vitro [1]. In glioma, CCL5 from glioma-associated microglia/macrophages regulated glioma migration and invasion via calcium-dependent matrix metalloproteinase 2 [2]. In chordoma, chordoma-secreted CCL5 promoted malignancy progression, macrophage recruitment, and M2 polarization, and CCL5 knockdown inhibited chordoma malignant progression [4]. In renal cancer, CCL5 promoted the epithelial-mesenchymal transition of circulating tumor cells, enhancing the malignant phenotype and lung metastasis [5].

In conclusion, Ccl5 plays a significant role in the development and progression of multiple cancers, including pancreatic, glioma, chordoma, and renal cancer. Studies using techniques like knockdown (functionally similar to loss-of-function in gene knockout models) have revealed its role in promoting tumor-related processes, providing potential therapeutic targets for these diseases.