Antitumor activity of alpha-galactosylceramide, KRN7000, in mice with the melanoma B16 hepatic metastasis and immunohistological study of tumor infiltrating cells.
Liver metastasis of primary tumors is clinically a major problem. We examined the antitumor activity of KRN7000, an alpha-galactosylceramide, in mice with liver metastasis of the B16 melanoma. KRN7000 significantly inhibited tumor growth in the liver, and its potency was similar to that of interleukin-12. The KRN7000 administration resulted in a high percentage of cured mice, which acquired tumor-specific immunity. To study what kinds of antitumor effector cells participated in killing tumor cells, we then performed immunohistological analysis of tumor-infiltrating cells, and found that KRN7000 induced marked invasion of NK1.1+ cells, CD8+ cells, and F4/80+ cells (macrophages) into B16 tumor nodules. In addition, it appeared that KRN7000-treated, liver-associated macrophages possessed strong lytic activity against tumor cells. These results suggest that NK cells, NK1.1+ T (NKT) cells, cytotoxic T lymphocytes, and macrophages play an important role in killing tumor cells in the liver, and that KRN7000 may be useful for the treatment of cancer liver metastasis.
Nakagawa
R
R
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
Serizawa
I
I
Motoki
K
K
Sato
M
M
Ueno
H
H
Iijima
R
R
Nakamura
H
H
Shimosaka
A
A
Koezuka
Y
Y
D000818:Animals; D000941:Antigens / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D000950:Antigens, Ly; D000954:Antigens, Surface; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D016827:CD8 Antigens / Q000378:metabolism; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology* / Q000627:therapeutic use*; D007150:Immunohistochemistry; D018664:Interleukin-12 / Q000494:pharmacology; D037181:Lectins, C-Type; D008113:Liver Neoplasms / Q000556:secondary; D008264:Macrophages / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011506:Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000941:Antigens; D000943:Antigens, Differentiation; D000950:Antigens, Ly; D000954:Antigens, Surface; D000970:Antineoplastic Agents; D016827:CD8 Antigens; D005699:Galactosylceramides; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D011994:Recombinant Proteins; C036763:monocyte-macrophage differentiation antigen; D018664:Interleukin-12; C103873:KRN 7000