| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Divisions of
*
Experimental Oncology D,
Medical Oncology B, and
Surgical Oncology B, Istituto Nazionale Tumori, Milan, Italy
Tumor cells have been shown recently to escape immune recognition by developing resistance to Fas-mediated apoptosis and acquiring expression of Fas ligand (FasL) molecule that they may use for eliminating activated Fas+ lymphocytes. In this study, we report that tumor-specific T lymphocytes isolated from tumor lesions by repeated in vitro TCR stimulation with relevant Ags (mostly represented by normal self proteins, such as MART-1/Melan A and gp100) can develop strategies for overcoming these escape mechanisms. Melanoma cells (and normal melanocytes) express heterogeneous levels of Fas molecule, but they result homogeneously resistant to Fas-induced apoptosis. However, CD4+ and CD8+ CTL clones kill melanoma cells through Fas/FasL-independent, granule-dependent lytic pathway. In these lymphocytes, Ag/MHC complex interaction with TCR does not lead to functional involvement of FasL, triggered, on the contrary, by T cell activation with nonspecific stimuli such as PMA/ionomycin. Additionally, melanoma cells express significant levels of FasL (detectable on the cell surface only after treatment with metalloprotease inhibitors), although to a lesser extent than professional immune cells such as Th1 clones. Nevertheless, antimelanoma CTL clones resist apoptosis mediated by FasL either in soluble form or expressed by Th1 lymphocytes or FasL+ melanoma cells. These results demonstrate that CD4+ and CD8+ antimelanoma T cell clones can be protected against Fas-dependent apoptosis, and thus be useful reagents of immunotherapeutic strategies aimed to potentiate tumor-specific T cell responses.
This article has been cited by other articles:
|
|
 |
|
  T. Lambe, J. C. H. Leung, T. Bouriez-Jones, K. Silver, K. Makinen, T. L. Crockford, H. Ferry, J. V. Forrester, and R. J. Cornall CD4 T Cell-Dependent Autoimmunity against a Melanocyte Neoantigen Induces Spontaneous Vitiligo and Depends upon Fas-Fas Ligand Interactions. J. Immunol., September 1, 2006; 177(5): 3055 - 3062. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Donskov, H. von der Maase, N. Marcussen, S. Hamilton-Dutoit, H. H. T. Madsen, J. J. Jensen, and M. Hokland Fas Ligand Expression in Metastatic Renal Cell Carcinoma During Interleukin-2 Based Immunotherapy: No In vivo Effect of Fas Ligand Tumor Counterattack Clin. Cancer Res., December 1, 2004; 10(23): 7911 - 7916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yang and F. G. Haluska Treatment of Melanoma with 5-Fluorouracil or Dacarbazine In Vitro Sensitizes Cells to Antigen-Specific CTL Lysis through Perforin/Granzyme- and Fas-Mediated Pathways J. Immunol., April 1, 2004; 172(7): 4599 - 4608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-L. Chen, S.-H. Chen, J.-Y. Wang, and B.-C. Yang Fas Ligand on Tumor Cells Mediates Inactivation of Neutrophils J. Immunol., August 1, 2003; 171(3): 1183 - 1191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Yanai, E. Ishii, K. Kojima, A. Hasegawa, T. Azuma, S. Hirose, N. Suga, A. Mitsudome, M. Zaitsu, Y. Ishida, et al. Essential Roles of Perforin in Antigen-Specific Cytotoxicity Mediated by Human CD4+ T Lymphocytes: Analysis Using the Combination of Hereditary Perforin-Deficient Effector Cells and Fas-Deficient Target Cells J. Immunol., February 15, 2003; 170(4): 2205 - 2213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Parmiani, C. Castelli, P. Dalerba, R. Mortarini, L. Rivoltini, F. M. Marincola, and A. Anichini Cancer Immunotherapy With Peptide-Based Vaccines: What Have We Achieved? Where Are We Going? J Natl Cancer Inst, June 5, 2002; 94(11): 805 - 818. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Andreola, L. Rivoltini, C. Castelli, V. Huber, P. Perego, P. Deho, P. Squarcina, P. Accornero, F. Lozupone, L. Lugini, et al. Induction of Lymphocyte Apoptosis by Tumor Cell Secretion of FasL-bearing Microvesicles J. Exp. Med., May 20, 2002; 195(10): 1303 - 1316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ugurel, G. Rappl, W. Tilgen, and U. Reinhold Increased Soluble CD95 (sFas/CD95) Serum Level Correlates with Poor Prognosis in Melanoma Patients Clin. Cancer Res., May 1, 2001; 7(5): 1282 - 1286. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. Chang, L. Galle, D. Maggs, D. M. Estes, and W. J. Mitchell Pathogenesis of Herpes Simplex Virus Type 1-Induced Corneal Inflammation in Perforin-Deficient Mice J. Virol., December 15, 2000; 74(24): 11832 - 11840. [Abstract] [Full Text]
|
|
|
|
|
|
C. Traidl, S. Sebastiani, C. Albanesi, H. F. Merk, P. Puddu, G. Girolomoni, and A. Cavani Disparate Cytotoxic Activity of Nickel-Specific CD8+ and CD4+ T Cell Subsets Against Keratinocytes J. Immunol., September 15, 2000; 165(6): 3058 - 3064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-H. Nam, H. Akari, K. Terao, H. Shibata, S. Kawamura, and Y. Yoshikawa Peripheral blood extrathymic CD4+CD8+ T cells with high cytotoxic activity are from the same lineage as CD4+CD8- T cells in cynomolgus monkeys Int. Immunol., July 1, 2000; 12(7): 1095 - 1103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Shankar, Z. Xu, and J. Lieberman Viral-Specific Cytotoxic T Lymphocytes Lyse Human Immunodeficiency Virus-Infected Primary T Lymphocytes by the Granule Exocytosis Pathway Blood, November 1, 1999; 94(9): 3084 - 3093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Shin, W. S. Park, S. Y. Kim, H. S. Kim, S. J. Kang, K. Y. Song, J. Y. Park, S. M. Dong, J. H. Pi, R. R. Oh, et al. Alterations of Fas (Apo-1/CD95) Gene in Cutaneous Malignant Melanoma Am. J. Pathol., June 1, 1999; 154(6): 1785 - 1791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Z. Zaks, D. B. Chappell, S. A. Rosenberg, and N. P. Restifo Fas-Mediated Suicide of Tumor-Reactive T Cells Following Activation by Specific Tumor: Selective Rescue by Caspase Inhibition J. Immunol., March 15, 1999; 162(6): 3273 - 3279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. B. Chappell, T. Z. Zaks, S. A. Rosenberg, and N. P. Restifo Human Melanoma Cells Do Not Express Fas (Apo-1/CD95) Ligand Cancer Res., January 1, 1999; 59(1): 59 - 62. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
