[Cancer Research 57, 2569-2574, July 1, 1997]
© 1997 American Association for Cancer Research
Protective Immunity Induced by Tumor Vaccines Requires Interaction between CD40 and Its Ligand, CD1541
Matthew F. Mackey,
Jason R. Gunn,
Patrick P. Ting,
Hitoshi Kikutani,
Glen Dranoff,
Randolph J. Noelle and
Richard J. Barth, Jr.2
Departments of Microbiology [M. F. M., R. J. N.] and Surgery [J. R. G., P. P. T., R. J. B.], Dartmouth Medical School and Norris Cotton Cancer Center, Lebanon, New Hampshire 03756; Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565, Japan [H. K.]; and Division of Clinical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115 [G. D.]
Interactions between CD40 and its ligand, CD154 (CD40L, gp39), have been shown to play a central role in the regulation of humoral immunity. Recent evidence suggests that this ligand-receptor pair also plays an important role in the induction of cell-mediated immune responses, including those directed against viral pathogens, intracellular parasites, and alloantigens. The contribution of this ligand-receptor pair to the development of protective immunity against syngeneic tumors was evaluated by blocking the in vivo function of CD154 or by studying tumor resistance in mice genetically deficient in CD40 expression (CD40-/-). In the former case, anti-CD154 monoclonal antibody treatment inhibited the generation of protective immune responses after the administration of three potent tumor vaccines: irradiated MCA 105, MCA 105 admixed with Corynebacterium parvum adjuvant, and irradiated B16 melanoma cells transduced with the gene for granulocyte macrophage colony-stimulating factor. Confirmation of the role of CD40/CD154 interactions in tumor immunity was provided by the overt tumor susceptibility in CD40-deficient mice as compared to that in CD40+/+ mice. In this case, wild-type but not CD40-deficient mice could be readily protected against live TS/A tumor challenge by preimmunization with TS/A admixed with C. parvum. These findings suggest a critical role for CD40/CD154 interactions in the induction of cellular immunity by tumor vaccines and may have important implications for future approaches to cell-based cancer therapies.
1 This work was supported by NIH Grants A126296 and A137075 (to R. J. N.) and an American Cancer Society Career Development Award (to R. J. B.).
2 To whom requests for reprints should be addressed, at Section of General Surgery, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756. Phone: (603) 650-7903; Fax: (603) 650-8030.
Received 4/21/97.
Accepted 5/13/97.
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Copyright © 1997 by the American Association for Cancer Research.
