Fractalkine Mediates Natural Killer-Dependent Antitumor Responses in Vivo

Elise Lavergne, Behazine Combadière, Olivia Bonduelle, Mutsunori Iga, Ji Liang Gao, Maud Maho, Alexandre Boissonnas, Philip M. Murphy, Patrice Debré, Christophe Combadière

Research output: Contribution to journalArticlepeer-review

85 Citations (Scopus)

Abstract

CX3CR1 has been described previously as a marker of human cytotoxic effector cells We evaluated the possibility of using its ligand, CX3CL1, to redirect immune response against tumors When murine lymphoma cell lines (EL4 and its derivative EG7) stably transfected with human-CX3CL1 were injected s.c. into C57BL/6 mice, the tumor growth was severely impaired when compared with the growth of control cell lines This antitumor effect of CX3CL1 was also found in T- and B-cell-deficient Rag1-/- mice but vanished in natural killer (NK) cell-deficient beige mice and in CX3CR1-/- mice, suggesting the involvement of CX3CR1-expressing NK cells. In addition, increased NK cell infiltration was observed in CX3CL1-producing tumors compared with controls. The effect of CX3CR1 on tumor growth required host cytotoxic effector cell functions because both IFNγ-/- and perforin-/- mice were resistant to CX3CLI antitumor effect Finally, intratumoral injection of DNA plasmid coding for a chimeric immunoglobulin presenting the CX3CL1 chemokine domain provided strong antitumor activity. Together, these data demonstrate that the CX3CL1 can reduce incidence and size of lymphoma in vivo through increased recruitment of activated NK cytotoxic cells These findings offer the first evidence of the potential of chimeric immunoglobulin-chemokines in anticancer therapy.

Original languageEnglish
Pages (from-to)7468-7474
Number of pages7
JournalCancer Research
Volume63
Issue number21
Publication statusPublished - Nov 1 2003

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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