caa a22 4500 397560524 CHVBK 20180308164815.0 cr unu---uuuuu 161202e19960403xx s 000 0 eng 10.1093/jnci/88.7.436 doi (NATIONALLICENCE)oxford-10.1093/jnci/88.7.436 Killing of Laminin Receptor-Positive Human Lung Cancers by Tumor-Infiltrating Lymphocytes Bearing γδ+ T-Cell Receptors [Elektronische Daten] [Marina Ferrarini, Silvia Heltai, Serenella M. Pupa, Sylvie Menard, M. Raffaella Zocchi] 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 γδ T-cell receptors. γδ+ 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 γδ+ 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 γδ+ T-cell infiltrates and from 11 other specimens infiltrated predominantly by lymphocytes bearing αβ T-cell receptors were analyzed for expression of the monomeric laminin receptor by use of the monoclonal antibody (MAb) MLuC5. γδ+ TILs and αβ+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 γδ T-cell receptors (i.e., TiγA 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 γδ+ 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 γδ+, but not αβ+, 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 γδ+ 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 γδ+ 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] © Oxford University Press REPORTS nationallicence Ferrarini Marina Laboratorio Immunoterapia Adottiva, Instituto Scientifico H. S. Raffaele Milan, Italy aut Heltai Silvia Laboratorio Immunoterapia Adottiva, Instituto Scientifico H. S. Raffaele Milan, Italy aut Pupa Serenella M. Oncologia Sperimentale E, Instituto Nationale per lo Studio e la Cura dei Tumori Milan aut Menard Sylvie Oncologia Sperimentale E, Instituto Nationale per lo Studio e la Cura dei Tumori Milan aut Zocchi M. Raffaella Laboratorio Immunoterapia Adottiva, Instituto Scientifico H. S. Raffaele Milan, Italy aut JNCI: Journal of the National Cancer Institute Oxford University Press 88/7(1996-04-03), 436-441 0027-8874 88:7<436 1996 88 jnci https://doi.org/10.1093/jnci/88.7.436 text/html Onlinezugriff via DOI 1 other jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jnci/88.7.436 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ferrarini Marina Laboratorio Immunoterapia Adottiva, Instituto Scientifico H. S. Raffaele Milan, Italy aut NATIONALLICENCE 700 1- Heltai Silvia Laboratorio Immunoterapia Adottiva, Instituto Scientifico H. S. Raffaele Milan, Italy aut NATIONALLICENCE 700 1- Pupa Serenella M. Oncologia Sperimentale E, Instituto Nationale per lo Studio e la Cura dei Tumori Milan aut NATIONALLICENCE 700 1- Menard Sylvie Oncologia Sperimentale E, Instituto Nationale per lo Studio e la Cura dei Tumori Milan aut NATIONALLICENCE 700 1- Zocchi M. Raffaella Laboratorio Immunoterapia Adottiva, Instituto Scientifico H. S. Raffaele Milan, Italy aut NATIONALLICENCE 773 0- JNCI: Journal of the National Cancer Institute Oxford University Press 88/7(1996-04-03), 436-441 0027-8874 88:7<436 1996 88 jnci Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford