| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Pediatric Oncology Branch, National Cancer Institute-Center for Cancer Research, Frederick, MD 21702;
Intramural Research Support Program and
Laboratory of Cell Mediated Immunity, SAIC-Frederick, Frederick, MD 21702; and
Department of Discovery Biology, DNAX Research Institute, Palo Alto, CA
We have shown previously that IFN-
-inducing cytokines such as IL-12 can mediate potent antitumor effects against murine solid tumors. IL-27 is a newly described IL-12-related cytokine that potentiates various aspects of T and/or NK cell function. We hypothesized that IL-27 might also mediate potent antitumor activity in vivo. TBJ neuroblastoma cells engineered to overexpress IL-27 demonstrated markedly delayed growth compared with control mice, and complete durable tumor regression was observed in >90% of mice bearing either s.c. or orthotopic intra-adrenal tumors, and 40% of mice bearing induced metastatic disease. The majority of mice cured of their original TBJ-IL-27 tumors were resistant to tumor rechallenge. Furthermore, TBJ-IL-27 tumors were heavily infiltrated by CD8+ T cells, and draining lymph node-derived lymphocytes from mice bearing s.c. TBJ-IL-27 tumors are primed to proliferate more readily when cultured ex vivo with anti-CD3/anti-CD28 compared with lymphocytes from mice bearing control tumors, and to secrete higher levels of IFN-. In addition, marked enhancement of local IFN- gene expression and potent up-regulation of cell surface MHC class I expression are noted within TBJ-IL-27 tumors compared with control tumors. Functionally, these alterations occur in conjunction with the generation of tumor-specific CTL reactivity in mice bearing TBJ-IL-27 tumors, and the induction of tumor regression via mechanisms that are critically dependent on CD8+, but not CD4+ T cells or NK cells. Collectively, these studies suggest that IL-27 could be used therapeutically to potentiate the host antitumor immune response in patients with malignancy.
This article has been cited by other articles:
|
|
 |
|
  D. Dibra, J. J. Cutrera, X. Xia, M. P. Birkenbach, and S. Li Expression of WSX1 in Tumors Sensitizes IL-27 Signaling-Independent Natural Killer Cell Surveillance Cancer Res., July 1, 2009; 69(13): 5505 - 5513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Salcedo, J. A. Hixon, J. K. Stauffer, R. Jalah, A. D. Brooks, T. Khan, R.-M. Dai, L. Scheetz, E. Lincoln, T. C. Back, et al. Immunologic and Therapeutic Synergy of IL-27 and IL-2: Enhancement of T Cell Sensitization, Tumor-Specific CTL Reactivity and Complete Regression of Disseminated Neuroblastoma Metastases in the Liver and Bone Marrow J. Immunol., April 1, 2009; 182(7): 4328 - 4338. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Matsui, T. Kishida, H. Nakano, K. Yoshimoto, M. Shin-Ya, T. Shimada, S. Nakai, J. Imanishi, T. Yoshimoto, Y. Hisa, et al. Interleukin-27 Activates Natural Killer Cells and Suppresses NK-Resistant Head and Neck Squamous Cell Carcinoma through Inducing Antibody-Dependent Cellular Cytotoxicity Cancer Res., March 15, 2009; 69(6): 2523 - 2530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yoshimoto, N. Morishima, I. Mizoguchi, M. Shimizu, H. Nagai, S. Oniki, M. Oka, C. Nishigori, and J. Mizuguchi Antiproliferative Activity of IL-27 on Melanoma J. Immunol., May 15, 2008; 180(10): 6527 - 6535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Liu, X. Guan, and X. Ma Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-{gamma}-mediated pathways J. Exp. Med., January 22, 2007; 204(1): 141 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Rutella, G. Bonanno, A. Procoli, A. Mariotti, D. G. de Ritis, A. Curti, S. Danese, G. Pessina, S. Pandolfi, F. Natoni, et al. Hepatocyte growth factor favors monocyte differentiation into regulatory interleukin (IL)-10++IL-12low/neg accessory cells with dendritic-cell features Blood, July 1, 2006; 108(1): 218 - 227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Oniki, H. Nagai, T. Horikawa, J. Furukawa, M. L. Belladonna, T. Yoshimoto, I. Hara, and C. Nishigori Interleukin-23 and interleukin-27 exert quite different antitumor and vaccine effects on poorly immunogenic melanoma. Cancer Res., June 15, 2006; 66(12): 6395 - 6404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shimizu, M. Shimamura, T. Owaki, M. Asakawa, K. Fujita, M. Kudo, Y. Iwakura, Y. Takeda, A. D. Luster, J. Mizuguchi, et al. Antiangiogenic and Antitumor Activities of IL-27. J. Immunol., June 15, 2006; 176(12): 7317 - 7324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Larousserie, P. Charlot, E. Bardel, J. Froger, R. A. Kastelein, and O. Devergne Differential Effects of IL-27 on Human B Cell Subsets J. Immunol., May 15, 2006; 176(10): 5890 - 5897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Khan, J. K. Stauffer, R. Williams, J. A. Hixon, R. Salcedo, E. Lincoln, T. C. Back, D. Powell, S. Lockett, A. C. Arnold, et al. Proteasome Inhibition to Maximize the Apoptotic Potential of Cytokine Therapy for Murine Neuroblastoma Tumors J. Immunol., May 15, 2006; 176(10): 6302 - 6312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Khan, J. A. Hixon, J. K. Stauffer, E. Lincoln, T. C. Back, J. Brenner, S. Lockett, K. Nagashima, D. Powell, and J. M. Wigginton Therapeutic Modulation of Akt Activity and Antitumor Efficacy of Interleukin-12 Against Orthotopic Murine Neuroblastoma J Natl Cancer Inst, February 1, 2006; 98(3): 190 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Villarino, J. Larkin III, C. J. M. Saris, A. J. Caton, S. Lucas, T. Wong, F. J. de Sauvage, and C. A. Hunter Positive and Negative Regulation of the IL-27 Receptor during Lymphoid Cell Activation J. Immunol., June 15, 2005; 174(12): 7684 - 7691. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
