| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
on APO2L/TRAIL Expression and -Mediated Cytotoxicity1
* Laboratoire Cytokines et Immunologie des Tumeurs Humaines, Institut National de la Santé et de la Recherche Médicale Unité 487, Institut Gustave Roussy, Villejuif, France;
Département de Chirurgie Thoracique, Institut Montsouris, Paris, France; and
Immunex Corporation, Seattle, WA 98101
In the present report, we have investigated TRAIL/APO2 ligand
(APO2L) expression, regulation, and function in human lung carcinoma
tumor-infiltrating lymphocytes. Using a panel of non-small cell lung
carcinoma cell lines, we first showed that most of them expressed
TRAIL-R1/DR4, TRAIL-R2/DR5, but not TRAIL-R3/DcR1 and TRAIL-R4/DcR2,
and were susceptible to APO2L/TRAIL-induced cell death. Two
APO2L/TRAIL-sensitive tumor cell lines (MHC class
I+/II+ or I+/II-) were
selected and specific CD4+ HLA-DR- or CD8+
HLA-A2-restricted CTL clones were respectively isolated from autologous
tumor-infiltrating lymphocytes. Interestingly, although the
established T cell clones did not constitutively express detectable
levels of APO2L/TRAIL, engagement of their TCR via activation with
specific tumor cells selectively induced profound APO2L/TRAIL
expression on the CD4+, but not on the CD8+,
CTL clones. Furthermore, as opposed to the CD8+ CTL clone
which mainly used granule exocytosis pathway, the CD4+ CTL
clone lysed the specific target via both perforin/granzymes and
APO2L/TRAIL-mediated mechanisms. The latter cytotoxicity
correlated with APO2L/TRAIL expression and was significantly enhanced
in the presence of IFN-
. More interestingly, in vivo studies
performed in SCID/nonobese diabetic mice transplanted with
autologous tumor and transferred with the specific CD4+ CTL
clone in combination with IFN- resulted in an important
APO2L/TRAIL-mediated tumor growth inhibition, which was prohibited by
soluble TRAIL-R2. Our findings suggest that APO2L/TRAIL, specifically
induced by autologous tumor and up-regulated by IFN-, may be a key
mediator of tumor-specific CD4+ CTL-mediated cell death and
point to a potent role of this T cell subset in tumor growth
control.
This article has been cited by other articles:
|
|
 |
|
  C. Jursik, M. Prchal, R. Grillari-Voglauer, K. Drbal, E. Fuertbauer, H. Jungfer, W. H. Albert, E. Steinhuber, T. Hemetsberger, J. Grillari, et al. Large-Scale Production and Characterization of Novel CD4+ Cytotoxic T Cells with Broad Tumor Specificity for Immunotherapy Mol. Cancer Res., March 1, 2009; 7(3): 339 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Umeshappa, H. Huang, Y. Xie, Y. Wei, S. J. Mulligan, Y. Deng, and J. Xiang CD4+ Th-APC with Acquired Peptide/MHC Class I and II Complexes Stimulate Type 1 Helper CD4+ and Central Memory CD8+ T Cell Responses J. Immunol., January 1, 2009; 182(1): 193 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hamai, F. Meslin, H. Benlalam, A. Jalil, M. Mehrpour, F. Faure, Y. Lecluse, P. Vielh, M.-F. Avril, C. Robert, et al. ICAM-1 Has a Critical Role in the Regulation of Metastatic Melanoma Tumor Susceptibility to CTL Lysis by Interfering with PI3K/AKT Pathway Cancer Res., December 1, 2008; 68(23): 9854 - 9864. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Le Maux Chansac, D. Misse, C. Richon, I. Vergnon, M. Kubin, J.-C. Soria, A. Moretta, S. Chouaib, and F. Mami-Chouaib Potentiation of NK cell-mediated cytotoxicity in human lung adenocarcinoma: role of NKG2D-dependent pathway Int. Immunol., July 1, 2008; 20(7): 801 - 810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Friedlein, F. El Hage, I. Vergnon, C. Richon, P. Saulnier, Y. Lecluse, A. Caignard, L. Boumsell, G. Bismuth, S. Chouaib, et al. Human CD5 Protects Circulating Tumor Antigen-Specific CTL from Tumor-Mediated Activation-Induced Cell Death J. Immunol., June 1, 2007; 178(11): 6821 - 6827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Floc'h, A. Jalil, I. Vergnon, B. L. M. Chansac, V. Lazar, G. Bismuth, S. Chouaib, and F. Mami-Chouaib {alpha}E{beta}7 integrin interaction with E-cadherin promotes antitumor CTL activity by triggering lytic granule polarization and exocytosis J. Exp. Med., March 19, 2007; 204(3): 559 - 570. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Cassatella, V. Huber, F. Calzetti, D. Margotto, N. Tamassia, G. Peri, A. Mantovani, L. Rivoltini, and C. Tecchio Interferon-activated neutrophils store a TNF-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand) intracellular pool that is readily mobilizable following exposure to proinflammatory mediators J. Leukoc. Biol., January 1, 2006; 79(1): 123 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Zerafa, J. A. Westwood, E. Cretney, S. Mitchell, P. Waring, M. Iezzi, and M. J. Smyth Cutting Edge: TRAIL Deficiency Accelerates Hematological Malignancies J. Immunol., November 1, 2005; 175(9): 5586 - 5590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Le Maux Chansac, A. Moretta, I. Vergnon, P. Opolon, Y. Lecluse, D. Grunenwald, M. Kubin, J.-C. Soria, S. Chouaib, and F. Mami-Chouaib NK Cells Infiltrating a MHC Class I-Deficient Lung Adenocarcinoma Display Impaired Cytotoxic Activity toward Autologous Tumor Cells Associated with Altered NK Cell-Triggering Receptors J. Immunol., November 1, 2005; 175(9): 5790 - 5798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Huang, T. Tatsumi, E. Pizzoferrato, N. Vujanovic, and W. J. Storkus Nitric Oxide Sensitizes Tumor Cells to Dendritic Cell-Mediated Apoptosis, Uptake, and Cross-Presentation Cancer Res., September 15, 2005; 65(18): 8461 - 8470. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kuwashima, F. Nishimura, J. Eguchi, H. Sato, M. Hatano, T. Tsugawa, T. Sakaida, J. E. Dusak, W. K. Fellows-Mayle, G. D. Papworth, et al. Delivery of Dendritic Cells Engineered to Secrete IFN-{alpha} into Central Nervous System Tumors Enhances the Efficacy of Peripheral Tumor Cell Vaccines: Dependence on Apoptotic Pathways J. Immunol., August 15, 2005; 175(4): 2730 - 2740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Dorothee, I. Vergnon, F. El Hage, B. L. M. Chansac, V. Ferrand, Y. Lecluse, P. Opolon, S. Chouaib, G. Bismuth, and F. Mami-Chouaib In Situ Sensory Adaptation of Tumor-Infiltrating T Lymphocytes to Peptide-MHC Levels Elicits Strong Antitumor Reactivity J. Immunol., June 1, 2005; 174(11): 6888 - 6897. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Spierings, E. G. de Vries, E. Vellenga, F. A. van den Heuvel, J. J. Koornstra, J. Wesseling, H. Hollema, and S. de Jong Tissue Distribution of the Death Ligand TRAIL and Its Receptors J. Histochem. Cytochem., June 1, 2004; 52(6): 821 - 831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Tecchio, V. Huber, P. Scapini, F. Calzetti, D. Margotto, G. Todeschini, L. Pilla, G. Martinelli, G. Pizzolo, L. Rivoltini, et al. IFN{alpha}-stimulated neutrophils and monocytes release a soluble form of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand) displaying apoptotic activity on leukemic cells Blood, May 15, 2004; 103(10): 3837 - 3844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. S. Schultz, B. Schuler-Thurner, V. Stroobant, L. Jenne, T. G. Berger, K. Thielemanns, P. van der Bruggen, and G. Schuler Functional Analysis of Tumor-Specific Th Cell Responses Detected in Melanoma Patients after Dendritic Cell-Based Immunotherapy J. Immunol., January 15, 2004; 172(2): 1304 - 1310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. J. Spierings, E. G. E. de Vries, W. Timens, H. J. M. Groen, H. M. Boezen, and S. de Jong Expression of TRAIL and TRAIL Death Receptors in Stage III Non-Small Cell Lung Cancer Tumors Clin. Cancer Res., August 1, 2003; 9(9): 3397 - 3405. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
