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Publication : CD154 inhibits tumor-induced apoptosis in dendritic cells and tumor growth.

First Author  Esche C Year  1999
Journal  Eur J Immunol Volume  29
Issue  7 Pages  2148-55
PubMed ID  10427977 Mgi Jnum  J:115301
Mgi Id  MGI:3691365 Doi  10.1002/(SICI)1521-4141(199907)29:07<2148::AID-IMMU2148>3.0.CO;2-F
Citation  Esche C, et al. (1999) CD154 inhibits tumor-induced apoptosis in dendritic cells and tumor growth. Eur J Immunol 29(7):2148-55
abstractText  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.
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