Vaccination of apoptotic Fas ligand-expressing tumors decreased antitumor responses by enhanced production of immunosuppressive cytokines

Anticancer Res. 2005 Jan-Feb;25(1A):299-303.

Abstract

Expression of Fas ligand (FasL) in tumors produced antitumor effects by generating both inflammation and T cell-mediated immunity, although the Fas/FasL interaction induces an apoptotic process of Fas-positive activated T cells. Our previous study, however, showed that immunization of mice with ultraviolet (UV)-treated FasL-expressing tumors rather induced immune suppression to the tumors, whereas mice rejected UV-untreated FasL-expressing tumors and developed protective immunity subsequently. Since dendritic cells (DCs) control tumor-specific immune responses in vivo, we examined a possible role of DCs in the immune suppression induced. Administration of DCs that were co-cultured with UV-treated FasL-expressing tumors did not influence the growth of parent tumors that were subsequently inoculated. Migration of immunocompetent cells into UV-treated FasL-expressing tumors was not significantly different from that into UV-untreated FasL-expressing tumors. However, production of immunosuppressive but not T helper type 1 cytokines was enhanced when UV-treated FasL-expressing tumors were administered. These data collectively suggest that the immune suppression induced by UV-treated FasL-expressing tumors was not attributable to tolerance of DCs, but due to cytokine-induced suppression of cell-mediated immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / pharmacology
  • Cell Movement / immunology
  • Cytokines / biosynthesis
  • Cytokines / immunology*
  • Dendritic Cells / immunology*
  • Fas Ligand Protein
  • Female
  • Immune Tolerance
  • Immunotherapy, Adoptive / methods
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / therapy
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes, Helper-Inducer / immunology
  • Ultraviolet Rays

Substances

  • Cancer Vaccines
  • Cytokines
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins