Antitumor effect after radiofrequency ablation of murine hepatoma is augmented by an active variant of CC Chemokine ligand 3/macrophage inflammatory protein-1alpha.
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.
Iida
Noriho
N
Disease Control and Homeostasis, Graduate School of Medical Science, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Nakamoto
Yasunari
Y
Baba
Tomohisa
T
Nakagawa
Hidetoshi
H
Mizukoshi
Eishiro
E
Naito
Makoto
M
Mukaida
Naofumi
N
Kaneko
Shuichi
S
D000818:Animals; D017115:Catheter Ablation; D045744:Cell Line, Tumor; D054405:Chemokine CCL3 / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D054389:Receptors, CCR1 / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
C515301:Ccr1 protein, mouse; D054405:Chemokine CCL3; D054389:Receptors, CCR1