Antitumor cytotoxic T-lymphocyte response in human lung carcinoma: identification of a tumor-associated antigen

Authors

  • Fathia Mami-Chouaib,

    1. Laboratoire Cytokines et Immunologie des tumeurs Humaines, U487 INSERM, Institut Fédératif de Recherche-54, Institut Gustave Roussy, Villejuif, France
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  • Hamid Echchakir,

    1. Laboratoire Cytokines et Immunologie des tumeurs Humaines, U487 INSERM, Institut Fédératif de Recherche-54, Institut Gustave Roussy, Villejuif, France
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  • Guillaume Dorothée,

    1. Laboratoire Cytokines et Immunologie des tumeurs Humaines, U487 INSERM, Institut Fédératif de Recherche-54, Institut Gustave Roussy, Villejuif, France
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  • Isabelle Vergnon,

    1. Laboratoire Cytokines et Immunologie des tumeurs Humaines, U487 INSERM, Institut Fédératif de Recherche-54, Institut Gustave Roussy, Villejuif, France
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  • Salem Chouaib

    1. Laboratoire Cytokines et Immunologie des tumeurs Humaines, U487 INSERM, Institut Fédératif de Recherche-54, Institut Gustave Roussy, Villejuif, France
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  • Fathia Mami-ChouaibHamid EchchakirGuillaume DorothéeIsabelle VergnonSalem Chouaib

Fathia Mami-Chouaib, Laboratoire ‘Cytokines et Immunologie des tumeurs humaines’, U487 INSERM, Institut Gustave Roussy, 39 rue Camille-Desmoulins, F-94 805 Villejuif, France.
Tel: + 33 1 42 11 49 65
Fax: + 33 1 42 11 52 88
e-mail: cfathia@igr.fr.

Abstract

Summary: We have isolated several cytotoxic T lymphocyte (CTL) clones from lymphocytes infiltrating a lung carcinoma of a patient with long survival. These clones showed a CD3+, CD8+, CD4, CD28 phenotype and expressed a T-cell receptor (TCR) encoded either by Vβ8-Jβ1.5 or Vβ22-Jβ1.4 rearrangements. Functional studies indicated that these clones mediated a high human leukocyte antigen (HLA)-A2.1-restricted cytotoxic activity against the autologous tumor cell line. Interestingly, TCRβ chain gene usage indicated that CTL clones identified in vitro were selectively expandedin vivo at the tumor site as compared to autologous peripheral blood lymphocytes (PBL). These findings provide evidence that an immune response may take place in non-small cell lung carcinoma and that effector T cells may contribute to tumor regression. Further study indicated that the CTL clones recognized the same decamer peptide encoded by a mutated α-actinin-4 gene. Using tetramers of soluble HLA-A2 molecules loaded with the mutated antigenic peptide, we have derived several anti-α-actinin-4 T-cell clones from patient PBL. These CTL, recognizing a truly tumor-specific antigen, may play a role in the clinical evolution of this lung cancer patient. Adoptive transfer of CTL clones in a SCID/NOD mice model transplanted with autologous tumor supported their antitumor effect in vivo.

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