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) V alpha/V beta 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 V alpha/V beta gene usage from these CTL was examined using the reversely transcribed-polymerase chain reaction method, demonstrating that the V alpha 7, V alpha 12, and V beta 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 V alpha 7, V alpha 12, and V beta 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 V alpha/V beta usage in 11 cases of in vivo tumor-infiltrating lymphocytes with this particular type of tumor. The data showed that V alpha 7, V alpha 12, V beta 6, and V beta 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 V alpha/V beta products could preferentially infiltrate into the stomach tissue, while some of these T-cells may be cytotoxic to the neoplastic autologous tumor cells.
Department of Pathology, Sapporo Medical University, School of Medicine, Japan.
H
H
Ikeda
N
N
Sato
A
A
Matsuura
K
K
Kikuchi
D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D001483:Base Sequence; D004381:Duodenal Ulcer / Q000235:genetics; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000378:metabolism; D007167:Immunotherapy; D008214:Lymphocytes / Q000502:physiology; D016246:Lymphocytes, Tumor-Infiltrating / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta