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

Abstract

Background: Adenosquamous carcinoma of the lung is not a common cancer, but its prognosis is worse than that of adenocarcinoma or squamous cell carcinoma. Therefore, new therapeutic strategies need to be developed to treat this type of lung cancer. Recently, vaccination using tumor antigens which are recognized by cytotoxic T lymphocytes (CTL) has been applied mainly to melanoma patients. We therefore attempted to establish T cell clones specific for autologous tumor cells (AT) from a patient with adenosquamous carcinoma in order to analyze the specific immune responses against AT. Methods: A lung adenosquamous carcinoma cell line was established from a resected tumor obtained from a 72-year-old patient. Regional lymph node lymphocytes were stimulated weekly with CD80-transfected AT to induce CTL. The CTL activities were assessed by a standard 51Cr release assay and by cytokine release. Results: We succeeded in inducing an AT-specific CTL line. Using a limiting dilution method, eight T cell clones were established. AT-specific activity was observed in three CD8+ T cell clones and one CD4+ T cell clone out of the eight clones tested. Anti-HLA class I and anti-HLA-B/C mAbs inhibited IFN-γ production from the AT-specific CD8+ clones co-cultured with AT, thus indicating the restriction element to be HLA-B*5201 or HLA-Cw*1202. In contrast, the CD4+ T cell clone recognized AT in an HLA class II-restricted manner. Conclusions: These results are the first demonstration of a successful induction of AT-specific T cell clones from a patient with lung adenosquamous carcinoma. It may therefore supply a possible way to apply specific immunotherapy to this type of lung cancer.