Antitumor Effect of CD40 Ligand: Elicitation of Local and Systemic Antitumor Responses by IL-12 and B7

• Published in: The Journal of immunology (1950) Vol. 161; no. 4; pp. 1901 - 1907
• Main Authors: Nakajima, Atsuo, Kodama, Tomohiro, Morimoto, Shinji, Azuma, Miyuki, Takeda, Kazuyoshi, Oshima, Hideo, Yoshino, Shin-ichi, Yagita, Hideo, Okumura, Ko
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.08.1998
• 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
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.161.4.1901

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.