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International Immunology, Vol. 12, No. 4, 537-546, April 2000
© 2000 Japanese Society for Immunology

Evidence for in situ expansion of diverse antitumor-specific cytotoxic T lymphocyte clones in a human large cell carcinoma of the lung

Hamid Echchakir, Isabelle Vergnon, Guillaume Dorothée, Dominique Grunenwald1, Salem Chouaib and Fathia Mami-Chouaib

Laboratoire Cytokines et Immunologie des tumeurs Humaines, U487 INSERM, Institut Gustave Roussy, 94805 Villejuif Cedex, France
1 Département Thoracique, Institut Montsouris, 75013 Paris, France

Correspondence to: F. Mami-Chouaib

We have isolated several cytotoxic T lymphocyte (CTL) clones from lymphocytes infiltrating a human large cell carcinoma (LCC) of the lung. All these clones were found to express a CD3+, TCR{alpha}ß+, CD8+, CD4, CD28 phenotype. According to their TCR ß chain variable region expression, they were divided in three major groups. The first group, including the majority of the clones, expressed a unique Vß3–Jß1.2 TCR. The second group expressed a Vß22–Jß1.4 rearrangement and the third group, including only two clones, expressed a Vß8–Jß1.5 TCR. Functional studies showed that all the CTL clones mediated a high cytotoxic activity against the autologous tumor cell line. While the Vß3+ clones showed a weak lysis against few allogeneic non-small cell lung cancer (NSCLC) tumor cell lines, Vß8+ and Vß22+ T cell clones were able to kill a panel of allogeneic NSCLC tumor cell lines. Cytotoxicity-blocking experiments using specific mAb indicated that, while the Vß3+ and Vß22+ CTL clones were HLA-A2 restricted, the Vß8+ clones appeared HLA-B or -C restricted. TCR transcripts expressed in the cloned cells were determined by CDR3 size and sequence analyses, and compared to those present in fresh tumor tissue. Interestingly, our studies demonstrated that the CTL clones identified in vitro were selectively expanded in vivo at the tumor site as compared to autologous peripheral blood lymphocytes. These results further provide evidence that an immune response may take place in NSCLC and that effector T cells may contribute to tumor regression.

Keywords: cytotoxic T lymphocyte, non-small cell lung cancer, TCR, tumor-associated antigen, tumor-infiltrating lymphocyte

Transmitting editor: J. F. Bach


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