Abstract
Objectives: C-C Motif Chemokine Ligand 5 (CCL5) is known for its role in immune regulation and has been implicated in cancer progression. However, its expression and prognostic significance in pan-cancer require comprehensive evaluation. This study was initiated to decipher the pan-cancer role of CCL5 genes. Methods: In silico analyses involving various online databases and molecular experiments involving CCL5 knockdown experiments in KIRC cell lines evaluated its role in cell proliferation, colony formation, and migration. Results: CCL5 expression was significantly up-regulated in several cancers. High CCL5 expression correlated with poorer overall survival in kidney renal cell carcinoma (KIRC) and esophageal cancer (ESCA) patients. Promoter hypomethylation correlated with elevated CCL5 expression and poorer prognosis. CCL5 mutations were rare; indicating its role in cancer is driven by overexpression rather than genetic alterations. Positive correlations with immune inhibitory and MHC genes suggested CCL5's role in fostering an immunosuppressive tumor microenvironment. High CCL5 expression correlated with increased immune cell infiltration, particularly CD8 T cells and macrophages. CCL5 expression did not significantly influence drug sensitivity. CCL5 knockdown in resulted in reduced proliferation, colony formation, and migration, underscoring its critical role in cancer cell dynamics. Conclusion: Our study highlights the significance of CCL5 in cancer progression and prognosis, particularly in KIRC and ESCA. CCL5's role in modulating the tumor immune microenvironment and its potential as a therapeutic target warrant further investigation.