PT  - JOURNAL ARTICLE
AU  - Smyth, Mark J.
AU  - Taniguchi, Masaru
AU  - Street, Shayna E. A.
TI  - The Anti-Tumor Activity of IL-12: Mechanisms of Innate Immunity That Are Model and Dose Dependent
AID  - 10.4049/jimmunol.165.5.2665
DP  - 2000 Sep 01
TA  - The Journal of Immunology
PG  - 2665--2670
VI  - 165
IP  - 5
4099  - http://www.jimmunol.org/content/165/5/2665.short
4100  - http://www.jimmunol.org/content/165/5/2665.full
SO  - J. Immunol.2000 Sep 01; 165
AB  - IL-12 has been demonstrated to have potent anti-tumor activities in a variety of mouse tumor models, but the relative roles of NK, NKT, and T cells and their effector mechanisms in these responses have not been fully addressed. Using a spectrum of gene-targeted or Ab-treated mice we have shown that for any particular tumor model the effector mechanisms downstream of IL-12 often mimic the natural immune response to that tumor. For example, metastasis of the MHC class I-deficient lymphoma, EL4-S3, was strictly controlled by NK cells using perforin either naturally or following therapy with high-dose IL-12. Intriguingly, in B16F10 and RM-1 tumor models both NK and NKT cells contribute to natural protection from tumor metastasis. In these models, a lower dose of IL-12 or delayed administration of IL-12 dictated a greater relative role of NKT cells in immune protection from tumor metastasis. Overall, both NK and NKT cells can contribute to natural and IL-12-induced immunity against tumors, and the relative role of each population is tumor and therapy dependent.