CD154 inhibits tumor-induced apoptosis in dendritic cells and tumor growth

Eur J Immunol. 1999 Jul;29(7):2148-55. doi: 10.1002/(SICI)1521-4141(199907)29:07<2148::AID-IMMU2148>3.0.CO;2-F.


We have recently demonstrated that murine and human tumors induce apoptosis of dendritic cells (DC). Here, we evaluated the effect of CD40 ligation on the survival of tumor-associated DC and tumor growth. Retroviral transduction of MC38 colon carcinoma cells with the CD154 gene resulted in inhibition of tumor growth. This effect was abrogated in IL-12 knockout mice. Immunohistochemical analysis revealed an increase in CD11c+ (N418) and CD8+ but not NLDC-145+ cells in CD154-transfected tumors in wild-type mice. This increase was less pronounced in IL-12-deficient mice. In vitro, overexpression of CD154 on tumor cells significantly decreased the level of tumor-induced DC apoptosis. Surprisingly, the CD154-induced protection of DC from tumor-induced apoptosis was IL-12 independent in vitro, suggesting an IL-12-dependent and an IL-12-independent mechanism of CD154-induced anti-tumor immunity. Thus, our data suggest a new strategy to improve immunotherapy of cancer by protecting DC from tumor-induced apoptosis.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • CD40 Ligand
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / pathology*
  • Colonic Neoplasms / therapy
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology*
  • Humans
  • Immunotherapy
  • Integrin alphaXbeta2 / metabolism
  • Interleukin-12 / genetics
  • Interleukin-12 / physiology
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Transduction, Genetic


  • Integrin alphaXbeta2
  • Membrane Glycoproteins
  • CD40 Ligand
  • Interleukin-12