T cell-dependent antitumor immunity mediated by secondary lymphoid tissue chemokine: Augmentation of dendritic cell-based immunotherapy

C. J. Kirk, Dennis Hartigan-O'Connor, B. J. Nickoloff, J. S. Chamberlain, M. Giedlin, L. Aukerman, J. J. Mulé

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

Secondary lymphoid tissue chemokine (SLC) is a CC chemokine that is selective in its recruitment of naïve T cells and dendritic cells (DCs). In the lymph node, SLC is believed to play an important role in the initiation of an immune response by colocalizing naïve T cells with DC-presenting antigen. Here, we used SLC as a treatment for tumors established from the poorly immunogenic B16 melanoma. Intratumoral injections of SLC inhibited tumor growth in a CD8+, T cell-dependent manner. SLC elicited a substantial infiltration of DCs and T cells into the tumor, coincident with the antitumor response. We next used SLC gene-modified DCs as a treatment of established tumors. Intratumoral injections of SLC-expressing DCs resulted in tumor growth inhibition that was significantly better than either control DCs or SLC alone. Distal site immunization of tumor-bearing mice with SLC gene-modified DCs pulsed with tumor lysate elicited an antitumor response whereas control DCs did not. We also found that s.c. injection of lysate-pulsed DCs expressing SLC promoted the migration of T cells to the immunization site. This report demonstrates that SLC can both induce antitumor responses and enhance the antitumor immunity elicited by DCs.

Original languageEnglish (US)
Pages (from-to)2062-2070
Number of pages9
JournalCancer Research
Volume61
Issue number5
StatePublished - Mar 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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