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Science 22 November 1996:
Vol. 274. no. 5291, pp. 1363 - 1366
DOI: 10.1126/science.274.5291.1363
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Reports

Melanoma Cell Expression of Fas(Apo-1/CD95) Ligand: Implications for Tumor Immune Escape

M. Hahne, D. Rimoldi, M. Schröter, P. Romero, M. Schreier, L. E. French, P. Schneider, T. Bornand, A. Fontana, D. Lienard, J.-C. Cerottini, J. Tschopp *

Malignant melanoma accounts for most of the increasing mortality from skin cancer. Melanoma cells were found to express Fas (also called Apo-1 or CD95) ligand (FasL). In metastatic lesions, Fas-expressing T cell infiltrates were proximal to FasL+ tumor cells. In vitro, apoptosis of Fas-sensitive target cells occurred upon incubation with melanoma tumor cells; and in vivo, injection of FasL+ mouse melanoma cells in mice led to rapid tumor formation. In contrast, tumorigenesis was delayed in Fas-deficient lpr mutant mice in which immune effector cells cannot be killed by FasL. Thus, FasL may contribute to the immune privilege of tumors.

M. Hahne, M. Schröter, P. Schneider, T. Bornand, J. Tschopp, Institute of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
D. Rimoldi, P. Romero, M. Schreier, J.-C. Cerottini, Ludwig Institute of Cancer Research, Lausanne branch, University of Lausanne, CH-1066 Epalinges, Switzerland.
L. E. French, Department of Dermatology, University of Geneva, Medical School, CH-1211 Geneva 4, Switzerland.
A. Fontana, Clinical Immunology, Department of Internal Medicine, University Hospital, CH-8044 Zürich, Switzerland.
D. Lienard, Centre Pluridisciplinaire d'Oncologie, CHUV, CH-1011 Lausanne, Switzerland.
*   To whom correspondence should be addressed. E-mail: jurg.tschopp{at}ib.unil.ch

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T. Waku, T. Fujiwara, J. Shao, T. Itoshima, T. Murakami, M. Kataoka, S. Gomi, J. A. Roth, and N. Tanaka (2000)
J. Immunol. 165, 5884-5890
   Abstract »    Full Text »    PDF »
Inhibition of Daxx-Mediated Apoptosis by Heat Shock Protein 27.
S. J. Charette, J. N. Lavoie, H. Lambert, and J. Landry (2000)
Mol. Cell. Biol. 20, 7602-7612
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CM101 Treatment Overrides Tumor-induced Immunoprivilege Leading to Apoptosis.
F. M. Yakes, B. D. Wamil, F. Sun, H.-P. Yan, C. E. Carter, and C. G. Hellerqvist (2000)
Cancer Res. 60, 5740-5746
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The Mechanism of Unresponsiveness to Circulating Tumor Antigen MUC1 Is a Block in Intracellular Sorting and Processing by Dendritic Cells.
E. M. Hiltbold, A. M. Vlad, P. Ciborowski, S. C. Watkins, and O. J. Finn (2000)
J. Immunol. 165, 3730-3741
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Frequency of Apoptosis of Tumor-infiltrating Lymphocytes Induced by Fas Counterattack in Human Colorectal Carcinoma and Its Correlation with Prognosis.
K. Okada, K. Komuta, S. Hashimoto, S. Matsuzaki, T. Kanematsu, and T. Koji (2000)
Clin. Cancer Res. 6, 3560-3564
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Adenoviral-Mediated Transfer of the TNF-Related Apoptosis-Inducing Ligand/Apo-2 Ligand Gene Induces Tumor Cell Apoptosis.
T. S. Griffith, R. D. Anderson, B. L. Davidson, R. D. Williams, and T. L. Ratliff (2000)
J. Immunol. 165, 2886-2894
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Constitutive Expression of Functional 4-1BB (CD137) Ligand on Carcinoma Cells.
H. R. Salih, S. G. Kosowski, V. F. Haluska, G. C. Starling, D. T. Loo, F. Lee, A. A. Aruffo, P. A. Trail, and P. A. Kiener (2000)
J. Immunol. 165, 2903-2910
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Human Acute Myeloid Leukemia CD34+/CD38- Progenitor Cells Have Decreased Sensitivity to Chemotherapy and Fas-induced Apoptosis, Reduced Immunogenicity, and Impaired Dendritic Cell Transformation Capacities.
R. T. Costello, F. Mallet, B. Gaugler, D. Sainty, C. Arnoulet, J.-A. Gastaut, and D. Olive (2000)
Cancer Res. 60, 4403-4411
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p53 Promotes Selection for Fas-mediated Apoptotic Resistance.
H. L. Maecker, C. Koumenis, and A. J. Giaccia (2000)
Cancer Res. 60, 4638-4644
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Functional characterization of an IL-7-dependent CD4+CD8alpha alpha + Th3-type malignant cell line derived from a patient with a cutaneous T-cell lymphoma.
E. Poszepczynska, M. Bagot, H. Echchakir, D. Martinvalet, M. Ramez, D. Charue, L. Boumsell, and A. Bensussan (2000)
Blood 96, 1056-1063
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{Delta}-9-Tetrahydrocannabinol Inhibits Antitumor Immunity by a CB2 Receptor-Mediated, Cytokine-Dependent Pathway.
L. X. Zhu, S. Sharma, M. Stolina, B. Gardner, M. D. Roth, D. P. Tashkin, and S. M. Dubinett (2000)
J. Immunol. 165, 373-380
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Proapoptotic Fas Ligand Is Expressed by Normal Kidney Tubular Epithelium and Injured Glomeruli.
C. LORZ, A. ORTIZ, P. JUSTO, S. GONZÁLEZ-CUADRADO, N. DUQUE, C. GÓMEZ-GUERRERO, and J. EGIDO (2000)
J. Am. Soc. Nephrol. 11, 1266-1277
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Sensitivity to Fas-Mediated Apoptosis Is Determined Below Receptor Level in Human Vascular Smooth Muscle Cells.
S.-W. Chan, L. Hegyi, S. Scott, N. R. B. Cary, P. L. Weissberg, and M. R. Bennett (2000)
Circ. Res. 86, 1038-1046
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Cutting Edge: The Tumor Counterattack Hypothesis Revisited: Colon Cancer Cells Do Not Induce T Cell Apoptosis Via the Fas (CD95, APO-1) Pathway.
N. Favre-Felix, A. Fromentin, A. Hammann, E. Solary, F. Martin, and B. Bonnotte (2000)
J. Immunol. 164, 5023-5027
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Deficiency of the Fas apoptosis pathway without Fas gene mutations is a familial trait predisposing to development of autoimmune diseases and cancer.
U. Ramenghi, S. Bonissoni, G. Migliaretti, S. DeFranco, F. Bottarel, C. Gambaruto, D. DiFranco, R. Priori, F. Conti, I. Dianzani, et al. (2000)
Blood 95, 3176-3182
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Endogenous Interleukin-18 Modulates Immune Escape of Murine Melanoma Cells by Regulating the Expression of Fas Ligand and Reactive Oxygen Intermediates.
D. Cho, H. Song, Y. M. Kim, D. Houh, D. Y. Hur, H. Park, D. Yoon, K. H. Pyun, W. J. Lee, M. Kurimoto, et al. (2000)
Cancer Res. 60, 2703-2709
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A High Number of Tumor-infiltrating Lymphocytes Are Associated with a Small Tumor Size, Low Tumor Stage, and a Favorable Prognosis in Operated Small Cell Lung Carcinoma.
A.-K. Eerola, Y. Soini, and P. Pääkkö (2000)
Clin. Cancer Res. 6, 1875-1881
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Opposing Effects of Transmembrane and Soluble Fas Ligand Expression on Inflammation and Tumor Cell Survival.
A. M. Hohlbaum, S. Moe, and A. Marshak-Rothstein (2000)
J. Exp. Med. 191, 1209-1220
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PACLITAXEL-INDUCED APOPTOSIS IN NON-SMALL CELL LUNG CANCER CELL LINES IS ASSOCIATED WITH INCREASED CASPASE-3 ACTIVITY.
T. L. Weigel, M. T. Lotze, P. K. Kim, A. A. Amoscato, J. D. Luketich, and C. Odoux (2000)
J. Thorac. Cardiovasc. Surg. 119, 795-803
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cdr2, a Target Antigen of Naturally Occurring Human Tumor Immunity, Is Widely Expressed in Gynecological Tumors.
J. C. Darnell, M. L. Albert, and R. B. Darnell (2000)
Cancer Res. 60, 2136-2139
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The IFN Regulatory Factor Family Participates in Regulation of Fas Ligand Gene Expression in T Cells.
W. A. Chow, J. J. Fang, and J.-K. Yee (2000)
J. Immunol. 164, 3512-3518
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