Premium
Inhibition of tumor metastasis by adoptive transfer of IL‐12‐activated Vα14 NKT cells
Author(s) -
Shin Tahiro,
Nakayama Toshinori,
Akutsu Yasunori,
Motohashi Shinichiro,
Shibata Youichi,
Harada Michishige,
Kamada Noriaki,
Shimizu Chiori,
Shimizu Eiko,
Saito Tsuyoshi,
Ochiai Takenori,
Taniguchi Masaru
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20010215)91:4<523::aid-ijc1087>3.0.co;2-l
Subject(s) - adoptive cell transfer , natural killer t cell , cytotoxic t cell , cancer research , interleukin 12 , immune system , melanoma , immunology , biology , metastasis , lymphokine activated killer cell , cytokine , interleukin 21 , t cell , in vitro , cancer , biochemistry , genetics
A unique lymphocyte lineage, the Vα14 NKT cells, expresses both NK1.1 and an invariant antigen receptor encoded by Vα14 and Jα281 gene segments. Vα14 NKT cells play crucial roles in various immune responses, including autoimmune diseases, allergic reactions and anti‐tumor immunity. Vα14 NKT cells were demonstrated to be essential for anti‐tumor effect of IL‐12 in vivo . Here, we report that adoptive transfer of IL‐12‐activated Vα14 NKT cells prevents hepatic metastasis of B16 melanoma. The injection of large amounts of IL‐2, IL‐4, and IFN‐γ, which are cytokines produced by activated Vα14 NKT cells, exhibited no significant inhibition of the metastasis of this melanoma. The cells prepared from the liver of IL‐12‐injected mice expressed a potent cytotoxic activity on B16 melanoma cells in vitro . Although the adoptive transfer of IL‐12‐activated Vα14 NKT cells prevents hepatic metastasis of B16 melanoma, activated NK cells from IL‐12‐injected RAG‐1 −/− mice failed to inhibit the metastasis of this melanoma. Thus, the anti‐tumor effect of IL‐12 can be replaced by adoptive transfer of IL‐12‐activated Vα14 NKT cells but not by IL‐12‐activated NK cells, suggesting a minor role of NK cells for the IL‐12‐mediated anti‐tumor effect in this experimental system. Moreover, our studies have suggested the involvement of direct cytotoxic mechanisms rather than cytokine‐mediated immune responses at the effector phase of the Vα14 NKT cell‐mediated anti‐tumor activity. © 2001 Wiley‐Liss, Inc.