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

Cancer Res. 2001 Mar 1;61(5):2062-70.

Abstract

Secondary lymphoid tissue chemokine (SLC) is a CC chemokine that is selective in its recruitment of naive 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 naive 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Chemokine CCL21
  • Chemokines / genetics
  • Chemokines / immunology
  • Chemokines / pharmacology
  • Chemokines, CC / genetics
  • Chemokines, CC / immunology*
  • Chemokines, CC / pharmacology
  • Dendritic Cells / immunology*
  • Dendritic Cells / physiology
  • Female
  • Genetic Therapy
  • Immunity, Cellular / drug effects
  • Immunity, Cellular / immunology
  • Immunotherapy, Adoptive
  • Injections, Intralesional
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL

Substances

  • Ccl21c protein, mouse
  • Chemokine CCL21
  • Chemokines
  • Chemokines, CC