Antitumor effect of CD40 ligand: elicitation of local and systemic antitumor responses by IL-12 and B7.
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.
Department of Immunology, Juntendo University, School of Medicine, Tokyo, Japan. Nakaji@med.juntendo.ac.jp
A
A
Nakajima
T
T
Kodama
S
S
Morimoto
M
M
Azuma
K
K
Takeda
H
H
Oshima
S
S
Yoshino
H
H
Yagita
K
K
Okumura
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000502:physiology*; D019013:CD40 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D023201:CD40 Ligand; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods; D018664:Interleukin-12 / Q000096:biosynthesis / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D012515:Mast-Cell Sarcoma / Q000276:immunology* / Q000517:prevention & control*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014162:Transfection / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D000970:Antineoplastic Agents; D018122:B7-1 Antigen; D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D018664:Interleukin-12