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-...

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Bibliographic Details
Published in:The Journal of immunology (1950) 1998-08, Vol.161 (4), p.1901-1907
Main Authors: Nakajima, Atsuo, Kodama, Tomohiro, Morimoto, Shinji, Azuma, Miyuki, Takeda, Kazuyoshi, Oshima, Hideo, Yoshino, Shin-ichi, Yagita, Hideo, Okumura, Ko
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
B7-1 Antigen - biosynthesis
B7-1 Antigen - physiology
CD40 Antigens - biosynthesis
CD40 Antigens - genetics
CD40 Antigens - metabolism
CD40 Ligand
Female
Graft Rejection - immunology
Immunotherapy, Adoptive - methods
Interleukin-12 - biosynthesis
Interleukin-12 - physiology
Killer Cells, Natural - immunology
Ligands
Lymphocyte Activation - drug effects
Macrophages, Peritoneal - immunology
Macrophages, Peritoneal - metabolism
Mast-Cell Sarcoma - immunology
Mast-Cell Sarcoma - prevention & control
Membrane Glycoproteins - biosynthesis
Membrane Glycoproteins - genetics
Membrane Glycoproteins - pharmacology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Nude
Neoplasm Transplantation
Transfection - immunology
Up-Regulation - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.161.4.1901