Antitumor effect of CD40 ligand: elicitation of local and systemic antitumor responses by IL-12 and B7 |
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Authors: | A Nakajima T Kodama S Morimoto M Azuma K Takeda H Oshima S Yoshino H Yagita K Okumura |
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Affiliation: | Department of Immunology, Juntendo University, School of Medicine, Tokyo, Japan. Nakaji@med.juntendo.ac.jp |
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Abstract: | The interaction between CD40 ligand (CD40L, CD154) and its receptor CD40 has been implicated in the establishment of cell-mediated immunity as well as humoral immune responses. To examine the role of CD40L in eliciting antitumor immunity, we introduced murine CD40L gene into P815 mastocytoma (CD40L-P815). CD40L-P815 cells underwent prompt rejection when inoculated s.c. into syngenic DBA/2 mice or athymic BALB/c nu/nu mice, which was mediated by NK cells and dependent on endogenous IL-12. The primary rejection of CD40L-P815 cells in DBA/2 mice elicited CD8+ T cell-mediated protective and systemic immunity against parental tumor cells, which was induced by CD4+ T cells and endogenous B7. These results indicated a potent antitumor effect of CD40L that is mediated by potentiation of host Ag-presenting cell functions, and introduction of CD40L will be useful as a new strategy of immuno-gene therapy against tumors. |
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