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

Toshiki Yajima, Hitoshi Nishimura, Worawidh Wajjwalku, Mamoru Harada, Hiroyuki Kuwano, Yasunobu Yoshikai

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    48 Citations (Scopus)

    Abstract

    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-asialoGMI 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.

    Original languageEnglish
    Pages (from-to)573-578
    Number of pages6
    JournalInternational Journal of Cancer
    Volume99
    Issue number4
    DOIs
    Publication statusPublished - Jun 1 2002

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    All Science Journal Classification (ASJC) codes

    • Oncology
    • Cancer Research

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