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

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 x 10(9)PFU/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.

• Authors: Hong Xin, Toshiaki Kikuchi, Sita Andarini, Shinya Ohkouchi, Takuji Suzuki, Toshihiro Nukiwa, Huqun, Koichi Hagiwara, Tasuku Honjo, Yasuo Saijo
• Journal: European journal of immunology (Eur J Immunol) Vol. 35 Issue 5 Pg. 1371-80 (May 2005) ISSN: 0014-2980 [Print] Germany
• PMID: 15789339 (Publication Type: Journal Article)

Chemical References

• Chemokine CX3CL1
• Chemokines, CX3C
• Cx3cl1 protein, mouse
• Membrane Proteins

Topics

• Animals
• Blotting, Western
• Cell Line, Tumor
• Chemokine CX3CL1
• Chemokines, CX3C (genetics, immunology)
• Flow Cytometry
• Genetic Therapy
• Killer Cells, Natural (immunology)
• Lymphocyte Subsets (immunology)
• Membrane Proteins (genetics, immunology)
• Mice
• Neoplasms (immunology)
• Reverse Transcriptase Polymerase Chain Reaction
• T-Lymphocytes (immunology)
• Transduction, Genetic