© 1996 by Oxford University Press
Journal of the National Cancer Institute, Vol. 88, No. 7, 436-441,
April 3, 1996
© 1996 Oxford University Press
Killing of Laminin Receptor-Positive Human Lung Cancers by Tumor-Infiltrating Lymphocytes Bearing 
+ T-Cell Receptors
Laboratorio Immunoterapia Adottiva, Instituto Scientifico H. S. Raffaele Milan, Italy
Oncologia Sperimentale E, Instituto Nationale per lo Studio e la Cura dei Tumori Milan
Correspondence to: Marina Ferrarini, M.D., Laboratorio Immunoterapia Adottiva, Instituto Scientifico H. S. Raffaele, Via Olgettina 60, 20132 Milan, Italy.
BACKGROUND: The monomeric laminin receptor, a 67-kd high-affinity laminin-binding protein, is expressed by a variety of normal cell types. Overexpression and abnormal surface distribution of this receptor have been demonstrated in tumor cells, where it appears to promote tumor invasion and metastasis. Previously, we reported the existence of an association between laminin receptor overexpression by lung cancer cells and the presence of tumor-infiltrating lymphocytes (TILs) bearing 
T-cell receptors. + lymphocytes represent a sizable fraction of the TILs in approximately one fourth of lung cancers analyzed thus far.
PURPOSE: The aim of this study was to determine whether + TILs might participate in the immune response against lung cancer through recognition of monomeric laminin receptors expressed by tumor cells.
METHODS: Tumor cells from 11 lung cancer specimens exhibiting sizable + T-cell infiltrates and from 11 other specimens infiltrated predominantly by lymphocytes bearing 
T-cell receptors were analyzed for expression of the monomeric laminin receptor by use of the monoclonal antibody (MAb) MLuC5. + TILs and +TILs derived from four tumors were each examined for cytotoxic activity toward lung cancer target cells by use of a standard 51 Cr-release assay and lung tumor cell lines expressing different levels of surface monomeric laminin receptor. The ability of MAbs directed against the laminin receptor (i.e., MLuC5) or against T-cell receptors (i.e., TiA and A13) as well as laminin peptides known to bind to the laminin receptor to inhibit TIL-mediated target cell lysis was also determined.
RESULTS: We confirmed that the association between overexpression of the monomeric laminin receptor by lung tumor cells and the presence of + TILs is statistically significant (two-sided P = .003; Fisher's exact test). We also observed a relationship between the levels of laminin receptor expression on cultured lung cancer cells and their susceptibility to specific lysis by +, but not +, TILs. This specific cell killing was not T-cell receptor mediated, but it was inhibited by addition of the anti-monomeric laminin receptor MAb MLuC5 and by a synthetic peptide corresponding to amino acids 2091–2108 of the laminin A chain.
CONCLUSIONS AND IMPLICATIONS: Our results indicate that + TILs localized at human lung cancer sites can kill tumor cells in a process that involves interaction with the monomeric laminin receptor. The infiltration of + TILs at lung tumor sites may represent a first line of defense against cells undergoing malignant transformation. [J Natl Cancer Inst 1996;88:436–41]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. S. Percival Grape Consumption Supports Immunity in Animals and Humans J. Nutr., September 1, 2009; 139(9): 1801S - 1805S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Devaud, E. Bilhere, S. Loizon, V. Pitard, C. Behr, J.-F. Moreau, J. Dechanet-Merville, and M. Capone Antitumor Activity of {gamma}{delta} T Cells Reactive against Cytomegalovirus-Infected Cells in a Mouse Xenograft Tumor Model Cancer Res., May 1, 2009; 69(9): 3971 - 3978. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Catellani, A. Poggi, A. Bruzzone, P. Dadati, J. L. Ravetti, M. Gobbi, and M. R. Zocchi Expansion of V{delta}1 T lymphocytes producing IL-4 in low-grade non-Hodgkin lymphomas expressing UL-16-binding proteins Blood, March 1, 2007; 109(5): 2078 - 2085. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Thompson and M. J. Rogers Bisphosphonates and {gamma}{delta} T-Cells: New Insights into Old Drugs IBMS BoneKEy, August 1, 2006; 3(8): 5 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sicard, S. Ingoure, B. Luciani, C. Serraz, J.-J. Fournie, M. Bonneville, J. Tiollier, and F. Romagne In Vivo Immunomanipulation of V{gamma}9V{delta}2 T Cells with a Synthetic Phosphoantigen in a Preclinical Nonhuman Primate Model J. Immunol., October 15, 2005; 175(8): 5471 - 5480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Corvaisier, A. Moreau-Aubry, E. Diez, J. Bennouna, J.-F. Mosnier, E. Scotet, M. Bonneville, and F. Jotereau V{gamma}9V{delta}2 T Cell Response to Colon Carcinoma Cells J. Immunol., October 15, 2005; 175(8): 5481 - 5488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Poggi, C. Venturino, S. Catellani, M. Clavio, M. Miglino, M. Gobbi, A. Steinle, P. Ghia, S. Stella, F. Caligaris-Cappio, et al. V{delta}1 T Lymphocytes from B-CLL Patients Recognize ULBP3 Expressed on Leukemic B Cells and Up-Regulated by Trans-Retinoic Acid Cancer Res., December 15, 2004; 64(24): 9172 - 9179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kabelitz, D. Wesch, E. Pitters, and M. Zoller Characterization of Tumor Reactivity of Human V{gamma}9V{delta}2 {gamma}{delta} T Cells In Vitro and in SCID Mice In Vivo J. Immunol., December 1, 2004; 173(11): 6767 - 6776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Lozupone, D. Pende, V. L. Burgio, C. Castelli, M. Spada, M. Venditti, F. Luciani, L. Lugini, C. Federici, C. Ramoni, et al. Effect Of Human Natural Killer and {gamma}{delta} T Cells on the Growth of Human Autologous Melanoma Xenografts in SCID Mice Cancer Res., January 1, 2004; 64(1): 378 - 385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Rohrer, A. L. Barsoum, D. L. Dyess, J. A. Tucker, and J. H. Coggin Jr. Human Breast Carcinoma Patients Develop Clonable Oncofetal Antigen-Specific Effector and Regulatory T Lymphocytes J. Immunol., June 1, 1999; 162(11): 6880 - 6892. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Sciorati, P. Rovere, M. Ferrarini, S. Heltai, A. A. Manfredi, and E. Clementi Autocrine Nitric Oxide Modulates CD95-induced Apoptosis in gamma delta T Lymphocytes J. Biol. Chem., September 12, 1997; 272(37): 23211 - 23215. [Abstract] [Full Text] [PDF]
|
|