Analysis of T-Cell Receptor V Region Gene Usage of Cytotoxic T-Lymphocytes and Tumor-infiltrating Lymphocytes Derived from Human Autologous Gastric Signet Ring Cell Carcinomas

To determine the T-cell receptor (TCR) Vα/Vβ gene usage of the human autologous gastric tumor-specific cytotoxic T-lymphocytes (CTLs), we first established two pairs of tumor cell lines, HST2 and SSTW, from the malignant peritoneal effusions of signet ring cell carcinomas and their peripheral blood lymphocyte-derived tumor-specific CD8-positive CTL lines, TcHST2 and TcSSTW. TCR Vα/Vβ gene usage from these CTL was examined using the reversely transcribed-polymerase chain reaction method, demonstrating that the Vα 7, Vα 12, and Vβ 20 transcripts were commonly detected. The fact that repeated antigenic stimulation by mixed lymphocyte-autologous tumor cell cultures brought about the specific cytolysis and the restricted TCR usage of TCR Vα 7, Vα 12, and Vβ 20 strongly suggests that these TCR V region products participated in T-cell-cancer interaction. This restricted TCR V gene usage in the gastric signet ring cell carcinomas led us to examine further the frequency of TCR Vα/Vβ usage in 11 cases of in vivo tumor-infiltrating lymphocytes with this particular type of tumor. The data showed that Vα 7, Vα 12, Vβ 6, and Vβ 20 were also predominantly expressed among these tumor-infiltrating lymphocytes in vivo. However, it seemed that T-cells with these TCR V region products are not specific for the gastric signet ring cell carcinomas, since they also frequently infiltrate into noncancerous lesions, such as peptic ulcers. These data may suggest that T-cells with certain TCR Vα/Vβ products could preferentially infiltrate into the stomach tissue, while some of these T-cells may be cytotoxic to the neoplastic autologous tumor cells.