| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75235
Human uveal melanoma arises in an immune privileged ocular environment in which both adaptive and innate immune effector mechanisms are suppressed. Uveal melanoma is the most common intraocular tumor in adults and is derived from tissues in the eye that produce macrophage migration-inhibitory factor (MIF), a cytokine that has recently been demonstrated to produce immediate inhibition of NK cell-mediated lytic activity. Although NK cell-mediated lysis of uveal melanomas is inhibited in the eye, melanoma cells that disseminate from the eye are at risk for surveillance by NK cells. Moreover, uveal melanoma cells demonstrate a propensity to metastasize to the liver, an organ with one of the highest levels of NK activity in the body. Therefore, we speculated that uveal melanomas produced MIF as a means of escaping NK cell-mediated lysis. Accordingly, seven primary uveal melanoma cell lines and two cell lines derived from uveal melanoma metastases were examined for their production of MIF. MIF was detected in melanoma culture supernatants by both ELISA and the classical bioassay of macrophage migration inhibition. Melanoma-derived MIF inhibited NK cell-mediated lysis of YAC-1 and uveal melanoma cells. Cell lines derived from uveal melanoma metastases produced approximately twice as much biologically active MIF as cultures from primary uveal melanomas. Inhibition of NK cell-mediated killing by uveal melanoma-derived MIF was specifically inhibited in a dose-dependent manner by anti-MIF Ab. The results suggest that human uveal melanoma cells maintain a microenvironment of immune privilege by secreting active MIF that protects against NK cell-mediated killing.
This article has been cited by other articles:
|
|
 |
|
  Q. Zhou, X. Yan, J. Gershan, R. J. Orentas, and B. D. Johnson Expression of Macrophage Migration Inhibitory Factor by Neuroblastoma Leads to the Inhibition of Antitumor T Cell Reactivity In Vivo J. Immunol., August 1, 2008; 181(3): 1877 - 1886. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Krockenberger, Y. Dombrowski, C. Weidler, M. Ossadnik, A. Honig, S. Hausler, H. Voigt, J. C. Becker, L. Leng, A. Steinle, et al. Macrophage Migration Inhibitory Factor Contributes to the Immune Escape of Ovarian Cancer by Down-Regulating NKG2D J. Immunol., June 1, 2008; 180(11): 7338 - 7348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hallermalm, K. Seki, A. De Geer, B. Motyka, R. C. Bleackley, M. J. Jager, C. J. Froelich, R. Kiessling, V. Levitsky, and J. Levitskaya Modulation of the Tumor Cell Phenotype by IFN-{gamma} Results in Resistance of Uveal Melanoma Cells to Granule-Mediated Lysis by Cytotoxic Lymphocytes J. Immunol., March 15, 2008; 180(6): 3766 - 3774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Li, H. Alizadeh, and J. Y. Niederkorn Differential Expression of Chemokine Receptors on Uveal Melanoma Cells and Their Metastases Invest. Ophthalmol. Vis. Sci., February 1, 2008; 49(2): 636 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W. Chen, T. Uno, and B. R. Ksander Tumor Escape Mutants Develop within an Immune-Privileged Environment in the Absence of T Cell Selection J. Immunol., July 1, 2006; 177(1): 162 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X-X He, J Yang, Y-W Ding, W Liu, Q-Y Shen, and H H-X Xia Increased epithelial and serum expression of macrophage migration inhibitory factor (MIF) in gastric cancer: potential role of MIF in gastric carcinogenesis Gut, June 1, 2006; 55(6): 797 - 802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Arcuri, M Cintorino, A Carducci, S Papa, M G Riparbelli, S Mangioni, A M Di Blasio, P Tosi, and P Vigano Human decidual natural killer cells as a source and target of macrophage migration inhibitory factor Reproduction, January 1, 2006; 131(1): 175 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Li, J. Y. Niederkorn, S. Neelam, and H. Alizadeh Resistance and Susceptibility of Human Uveal Melanoma Cells to TRAIL-Induced Apoptosis Arch Ophthalmol, May 1, 2005; 123(5): 654 - 661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-G. He, E. Mayhew, J. Mellon, and J. Y. Niederkorn Expression and Possible Function of IL-2 and IL-15 Receptors on Human Uveal Melanoma Cells Invest. Ophthalmol. Vis. Sci., December 1, 2004; 45(12): 4240 - 4246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Ren, E. Mayhew, C. Hay, H. Li, H. Alizadeh, and J. Y. Niederkorn Uveal Melanoma Expression of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Receptors and Susceptibility to TRAIL-Induced Apoptosis Invest. Ophthalmol. Vis. Sci., April 1, 2004; 45(4): 1162 - 1168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ardjomand, N. Ardjomand, G. Schaffler, H. Radner, and Y. El-Shabrawi Expression of Somatostatin Receptors in Uveal Melanomas Invest. Ophthalmol. Vis. Sci., March 1, 2003; 44(3): 980 - 987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Arndt, G. Wennemuth, P. Barth, M. Nain, Y. Al-Abed, A. Meinhardt, D. Gemsa, and M. Bacher Release of Macrophage Migration Inhibitory Factor and CXCL8/Interleukin-8 from Lung Epithelial Cells Rendered Necrotic by Influenza A Virus Infection J. Virol., August 12, 2002; 76(18): 9298 - 9306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. H. Hurks, M. M. Valter, L. Wilson, I. Hilgert, P. J. van den Elsen, and M. J. Jager Uveal Melanoma: No Expression of HLA-G Invest. Ophthalmol. Vis. Sci., December 1, 2001; 42(13): 3081 - 3084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Ericsson, S. Seregard, A. Bartolazzi, E. Levitskaya, S. Ferrone, R. Kiessling, and O. Larsson Association of HLA Class I and Class II Antigen Expression and Mortality in Uveal Melanoma Invest. Ophthalmol. Vis. Sci., September 1, 2001; 42(10): 2153 - 2156. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
