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. |