Killing of laminin receptor-positive human lung cancers by tumor-infiltrating lymphocytes bearing γδ+ T-cell receptors

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Abstract

Background: The monomeric laminin receptor, a 67-kd high-affinity lamininbinding 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 51Cr-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., MLuCS) 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 (twosided 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 MLuCS 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.

Original languageEnglish
Pages (from-to)436-441
Number of pages6
JournalJournal of the National Cancer Institute
Volume88
Issue number7
Publication statusPublished - Apr 3 1996

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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