CCL5 is a C-C motif chemokine that functions as a multifaceted immune regulator with critical roles in both antitumor immunity and cancer progression. Primarily, CCL5 acts as a chemoattractant for monocytes, T cells, and eosinophils 1, and serves as one of the major HIV-suppressive factors produced by CD8+ T cells [UniProt]. In the tumor microenvironment, CCL5 demonstrates dichotomous functions. NK cells produce CCL5 to recruit conventional type 1 dendritic cells (cDC1), promoting antitumor immunity and correlating with improved patient survival 2. Conversely, CCL5 secreted by tumor cells promotes malignant progression through multiple mechanisms: it recruits and polarizes macrophages toward immunosuppressive M2 phenotypes in lung adenocarcinoma, chordoma, and glioma 345, and facilitates tumor cell migration and invasion via calcium-dependent matrix metalloproteinase 2 activation and ERK pathway signaling 56. In pancreatic cancer, CCL5 interacts with SDC1 on tumor cells to promote migration 7. High CCL5/CCR5 axis expression correlates with immunosuppressive immune infiltration and poor colorectal cancer outcomes 8. Notably, CCL5/CCR5 appears dispensable for monocyte recruitment in osteoarthritis, where CCL2/CCR2 predominates 1, highlighting context-dependent chemokine hierarchy.