Generation of autologous tumor-specific T cell clones from a patient with adenosquamous carcinoma of the lung

Background: Adenosquamous carcinoma of the lung is not a common cancer, but its prognosis is worse than that of adenocarcinoma or squamous cell carcin oma. Therefore, new therapeutic strategies need to be developed to treat th is type of lung cancer. Recently, vaccination using tumor antigens which ar e recognized by cytotoxic T lymphocytes (CTL) has been applied mainly to me lanoma patients. We therefore attempted to establish T cell clones specific for autologous tumor cells (AT) from a patient with adenosquamous carcinom a in order to analyze the specific immune responses against AT. Methods: A lung adenosquamous carcinoma cell line was established from a re sected tumor obtained from a 72-year-old patient. Regional lymph node lymph ocytes were stimulated weekly with CD80-transfected AT to induce CTL. The C TL activities were assessed by a standard Cr-51 release assay and by cytoki ne release. Results: We succeeded in inducing an AT-specific CTL line. Using a limiting dilution method, eight T cell clones were established. AT-specific activit y was observed in three CD8(+) T cell clones and one CD4(+) T cell clone ou t of the eight clones tested. Anti-HLA class I and anti-HLA-B/C mAbs inhibi ted IFN-gamma production from the AT-specific CD8(+) clones co-cultured wit h AT, thus indicating the restriction element to be HLA-B*5201 or HLA-Cw*12 02. In contrast, the CD4(+) T cell clone recognized AT in an HLA class II-r estricted manner. Conclusions: These results are the first demonstration of a successful indu ction of AT-specific T cell clones from a patient with lung adenosquamous c arcinoma. It may therefore supply a possible way to apply specific immunoth erapy to this type of lung cancer.