Immunological and Antitumor Effects of IL-23 as a Cancer Vaccine Adjuvant

W.W. Overwijk*, K.E. de Visser, F.H. Tirion, L.A. de Jong, T.W. Pols, Y.U. van der Velden, J.G. van den Boorn, A.M. Keller, W.A. Buurman, M.R. Theoret, B. Blom, N.P. Restifo, A.M. Kruisbeek, R.A. Kastelein, J.B. Haanen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


The promising, but modest, clinical results of many human cancer vaccines indicate a need for vaccine adjuvants that can increase both the quantity and the quality of vaccine-induced, tumor-specific T cells. In this study we tested the immunological and antitumor effects of the proinflammatory cytokine, IL-23, in gp100 peptide vaccine therapy of established murine melanoma. Neither systemic nor local IL-23 alone had any impact on tumor growth or tumor-specific T cell numbers. Upon specific vaccination, however, systemic IL-23 greatly increased the relative and absolute numbers of vaccine-induced CD8(+) T cells and enhanced their effector function at the tumor site. Although IL-23 specifically increased IFN-gamma production by tumor-specific T cells, IFN-gamma itself was not a primary mediator of the vaccine adjuvant effect. The IL-23-induced antitumor effect and accompanying reversible weight loss were both partially mediated by TNF-alpha. In contrast, local expression of IL-23 at the tumor site maintained antitumor activity in the absence of weight loss. Under these conditions, it was also clear that enhanced effector function of vaccine-induced CD8(+) T cells, rather than increased T cell number, is a primary mechanism underlying the antitumor effect of IL-23. Collectively, these results suggest that IL-23 is a potent vaccine adjuvant for the induction of therapeutic, tumor-specific CD8(+) T cell responses
Original languageEnglish
Pages (from-to)5213-5222
JournalJournal of Immunology
Issue number9
Publication statusPublished - 1 Jan 2006


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