Overexpression of interleukin-15 in vivo enhances antitumor activity against MHC class I-negative and -positive malignant melanoma through augmented NK activity and cytotoxic T-cell response.
Interleukin (IL)-15, a pleiotropic cytokine, is involved in the development and maintenance of NK cells and memory CD8+ T cells. We examined the effects of in vivo overexpression of IL-15 on protection against 2 types of murine B16 melanoma lines, MHC class I-negative B16.44 and MHC class I-positive B16F10 cells, using IL-15 transgenic (Tg) mice that we have recently constructed. The tumor growth was severely retarded in IL-15 Tg mice after subcutaneous (s.c.) inoculation with B16.44 or B16F10 cells. IL-15 Tg mice showed an augmented NK cell activity against B16.44 cells, and in vivo depletion of NK cells by anti-asialoGM1 Ab treatment abrogated the antitumor activity in IL-15 Tg mice. On the other hand, IL-15 Tg mice inoculated with B16F10 cells developed a significant level of CTL response against B16F10 cells, and in vivo depletion of CD8+ T cells by anti-CD8 MAb treatment abrogated the antitumor activity. Thus, overexpression of IL-15 augmented antitumor activity against different tumors via augmentation of different antitumor mechanisms. These results suggest a possible therapeutic application of IL-15 for human neoplasms expressing a wide range of MHC class molecules.
Yajima
Toshiki
T
Laboratory of Host Defense and Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya 466-8550, Japan.
Nishimura
Hitoshi
H
Wajjwalku
Worawidh
W
Harada
Mamoru
M
Kuwano
Hiroyuki
H
Yoshikai
Yasunobu
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D005805:Genes, MHC Class I / Q000235:genetics*; D007074:Immunoglobulin G / Q000378:metabolism; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000378:metabolism*; D008285:Major Histocompatibility Complex; D008545:Melanoma / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009369:Neoplasms / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D019409:Interleukin-15