Several
chemokines are used for
immunotherapy against
cancers because they can attract immune cells such as dendritic and cytotoxic T cells to augment immune responses.
Radiofrequency ablation (RFA) is used to locally eliminate
cancers such as
hepatocellular carcinoma (HCC),
renal cell carcinoma, and
lung cancer. Because HCC often recurs even after an eradicative treatment with RFA, additional
immunotherapy is necessary. We treated
tumor-bearing mice by administering ECI301, an active variant of
CC chemokine ligand 3, after RFA. Mice were injected s.c. with BNL 1ME A.7R.1, a murine
hepatoma cell line, in the bilateral flank. After the
tumor became palpable, RFA was done on the
tumor of one flank with or without ECI301. RFA alone eliminated the treated ipsilateral
tumors and retarded the growth of contralateral non-RFA-treated
tumors accompanied by massive T-cell infiltration. Injection of ECI301 augmented RFA-induced antitumor effect against non-RFA-treated
tumors when administered to wild-type or CCR5-deficient but not CCR1-deficient mice. ECI301 also increased CCR1-expressing CD11c(+) cells in peripheral blood and RFA-treated
tumors after RFA. Deficiency of CCR1 impairs accumulation of CD11c(+), CD4(+), and CD8(+) cells in RFA-treated
tumors. Furthermore, in IFN-gamma-
enzyme-linked immunospot assay, ECI301 augmented
tumor-specific responses after RFA whereas deficiency of CCR1 abolished this augmentation. Thus, we proved that ECI301 further augments RFA-induced antitumor immune responses in a CCR1-dependent manner.