Antitumor immune response by CX3CL1 fractalkine gene transfer depends on both NK and T cells

Hong Xin, Toshiaki Kikuchi, Sita Andarini, Shinya Ohkouchi, Takuji Suzuki, Toshihiro Nukiwa, Huqun, Koichi Hagiwara, Tasuku Honjo, Yasuo Saijo

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

The CX3C chemokine fractalkine (CX3CL1) exists as both a membrane-bound form promoting firm cell-cell adhesion and a soluble form chemoattracting leukocytes expressing its receptor CX3CR1. When adenoviral vector expressing mouse fractalkine (AdFKN) was transduced to the tumor cells, fractalkine was expressed as both membrane-bound form on the tumor cells and soluble form in the supernatant in vitro. Intratumoral injection of AdFKN (1 × 109PFU/tumor) into C26 and B16F10 tumors resulted in marked reduction of tumor growth compared to control (C26: 86.5%, p<0.001; B16F10: 85.5%, p<0.001). Histological examination of tumor tissues revealed abundant infiltration of NK cells, dendritic cells, and CD8+ T lymphocytes 3 and/or 6 days after treatment with AdFKN. Splenocytes from mice treated by AdFKN developed tumor-specific cytotoxic T cells, and thereby protected from rechallenging with parental tumor cells. Antitumor effects by AdFKN were completely abrogated in both NK cell-depleted mice and CD8-/- mice, and partially blocked in CD4-/- mice. These data indicated that fractalkine mediates antitumor effects by both NK cell-dependent and T cell-dependent mechanisms. This study suggests that fractalkine can be a suitable candidate for immunogene therapy of cancer because fractalkine induces both innate and adaptive immunity.

Original languageEnglish
Pages (from-to)1371-1380
Number of pages10
JournalEuropean Journal of Immunology
Volume35
Issue number5
DOIs
Publication statusPublished - 2005 May

Keywords

  • Chemokine
  • Fractalkine
  • Gene therapy
  • NK cells
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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