Enhancement of anti-tumor immunity by tumor cells transfected with the secondary lymphoid tissue chemokine EBI-1-ligand chemokine and stromal cell-derived factor-1alpha chemokine genes

Int J Cancer. 2001 Mar 1;91(5):597-606. doi: 10.1002/1097-0215(200002)9999:9999<::aid-ijc1107>3.0.co;2-j.

Abstract

Several new lymphocyte-specific chemokines, which attract naive and memory T cells, B cells, dendritic cells and natural killer cells, have been isolated. We have found evidence of the anti-tumor effects of 3 major lymphocyte-specific chemokines, secondary lymphoid tissue chemokine (SLC), EBI-1-ligand chemokine (ELC) and stromal cell-derived factor (SDF)-1alpha, in murine models (Meth A fibrosarcoma and HM-1 ovarian tumor). In both naive and immunized mice, tumors expressing SLC, ELC or SDF-1alpha showed delayed progression compared with control tumors. In mice immunized with tumor cells expressing 1 of these 3 chemokine genes, challenge with parental tumor cells resulted in slightly slower progression than in control mice, while in mice immunized with tumor cells transfected to co-express IL-2 or granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as these chemokines, all tumors regressed. Furthermore, spleen cells from mice immunized with these "double-transfected" tumor cells exhibited higher proliferative responses and greater cytotoxic activity against parental tumor cells. These anti-tumor effects were associated with profound alterations in the leukocyte populations within the tumors and regional lymph nodes, and this was due to activation of type I T cell-dependent responses that produced high levels of IFN-gamma. These findings show that SLC, ELC and SDF-1alpha enhance anti-tumor immunity both systemically and locally and that these chemokines may be clinically useful, especially when combined with IL-2 and GM-CSF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / metabolism
  • Cancer Vaccines*
  • Cell Division
  • Chemokine CCL19
  • Chemokine CCL21
  • Chemokine CXCL12
  • Chemokines, CC / genetics*
  • Chemokines, CXC / genetics*
  • Disease Progression
  • Female
  • Genetic Therapy / methods*
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / genetics
  • Interleukin-4 / biosynthesis
  • Killer Cells, Natural / metabolism
  • Leukocytes / metabolism
  • Lymph Nodes / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Neoplasm Transplantation
  • Phenotype
  • Spleen / cytology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Time Factors
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Cancer Vaccines
  • Ccl19 protein, mouse
  • Ccl21c protein, mouse
  • Chemokine CCL19
  • Chemokine CCL21
  • Chemokine CXCL12
  • Chemokines, CC
  • Chemokines, CXC
  • Cxcl12 protein, mouse
  • Interleukin-2
  • Interleukin-4
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor