TY - JOUR
T1 - Immunological and antitumor effects of IL-23 as a cancer vaccine adjuvant
AU - Overwijk, Willem W.
AU - De Visser, Karin E.
AU - Tirion, Felicia H.
AU - De Jong, Laurina A.
AU - Pols, Thijs W.H.
AU - Van Der Velden, Yme U.
AU - Van Den Boorn, Jasper G.
AU - Keller, Anna M.
AU - Buurman, Wim A.
AU - Theoret, Marc R.
AU - Blom, Bianca
AU - Restifo, Nicholas P.
AU - Kruisbeek, Ada M.
AU - Kastelein, Robert A.
AU - Haanen, John B.A.G.
PY - 2006/5/1
Y1 - 2006/5/1
N2 - 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-γ production by tumor-specific T cells, IFN-γ 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-γ. 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.
AB - 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-γ production by tumor-specific T cells, IFN-γ 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-γ. 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.
UR - http://www.scopus.com/inward/record.url?scp=33645972617&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645972617&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.176.9.5213
DO - 10.4049/jimmunol.176.9.5213
M3 - Article
C2 - 16621986
AN - SCOPUS:33645972617
SN - 0022-1767
VL - 176
SP - 5213
EP - 5222
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -