IL-18 inhibits growth of murine orthotopic prostate carcinomas via both adaptive and innate immune mechanisms.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractInterleukin(IL)-18 is a pleiotrophic cytokine with functions in immune modulation, angiogenesis and bone metabolism. In this study, the potential of IL-18 as an immunotherapy for prostate cancer (PCa) was examined using the murine model of prostate carcinoma, RM1 and a bone metastatic variant RM1(BM)/B4H7-luc. RM1 and RM1(BM)/B4H7-luc cells were stably transfected to express bioactive IL-18. These cells were implanted into syngeneic immunocompetent mice, with or without an IL-18-neutralising antibody (αIL-18, SK113AE4). IL-18 significantly inhibited the growth of both subcutaneous and orthotopic RM1 tumors and the IL-18 neutralizing antibody abrogated the tumor growth-inhibition. In vivo neutralization of interferon-gamma (IFN-γ) completely eliminated the anti-tumor effects of IL-18 confirming an essential role of IFN-γ as a down-stream mediator of the anti-tumor activity of IL-18. Tumors from mice in which IL-18 and/or IFN-γ was neutralized contained significantly fewer CD4(+) and CD8(+) T cells than those with functional IL-18. The essential role of adaptive immunity was demonstrated as tumors grew more rapidly in RAG1(-/-) mice or in mice depleted of CD4(+) and/or CD8(+) cells than in normal mice. The tumors in RAG1(-/-) mice were also significantly smaller when IL-18 was present, indicating that innate immune mechanisms are involved. IL-18 also induced an increase in tumor infiltration of macrophages and neutrophils but not NK cells. In other experiments, direct injection of recombinant IL-18 into established tumors also inhibited tumor growth, which was associated with an increase in intratumoral macrophages, but not T cells. These results suggest that local IL-18 in the tumor environment can significantly potentiate anti-tumor immunity in the prostate and clearly demonstrate that this effect is mediated by innate and adaptive immune mechanisms.
CitationIL-18 inhibits growth of murine orthotopic prostate carcinomas via both adaptive and innate immune mechanisms. 2011, 6 (9):e24241 PLoS ONE
AffiliationLowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales, Australia.
The following license files are associated with this item:
- IL-15 has innate anti-tumor activity independent of NK and CD8 T cells.
- Authors: Davies E, Reid S, Medina MF, Lichty B, Ashkar AA
- Issue date: 2010 Sep
- Adenovirus-mediated interleukin-18 mutant in vivo gene transfer inhibits tumor growth through the induction of T cell immunity and activation of natural killer cell cytotoxicity.
- Authors: Hwang KS, Cho WK, Yoo J, Seong YR, Kim BK, Kim S, Im DS
- Issue date: 2004 Jun
- TARC and RANTES enhance antitumor immunity induced by the GM-CSF-transduced tumor vaccine in a mouse tumor model.
- Authors: Inoue H, Iga M, Xin M, Asahi S, Nakamura T, Kurita R, Nakayama M, Nakazaki Y, Takayama K, Nakanishi Y, Tani K
- Issue date: 2008 Sep
- Cancer immunotherapy with interleukin 12 and granulocyte-macrophage colony-stimulating factor-encapsulated microspheres: coinduction of innate and adaptive antitumor immunity and cure of disseminated disease.
- Authors: Hill HC, Conway TF Jr, Sabel MS, Jong YS, Mathiowitz E, Bankert RB, Egilmez NK
- Issue date: 2002 Dec 15
- Angiostatin anti-angiogenesis requires IL-12: the innate immune system as a key target.
- Authors: Albini A, Brigati C, Ventura A, Lorusso G, Pinter M, Morini M, Mancino A, Sica A, Noonan DM
- Issue date: 2009 Jan 14