Profile of T-cell receptor V beta gene usage of cytotoxic T cells induced by intrapleural administration of a streptococcal preparation, OK432, in malignant effusions.
T-cell receptor (TCR) gene rearrangements were analyzed in tumor-infiltrating lymphocytes (TIL) using the reverse transcription-polymerase chain reaction (RT-PCR) to determine whether oligoclonal expression of TCRV beta occurs in TIL, and if so, whether it is involved in the clinical response and mechanisms of locoregional immunotherapy using a streptococcal preparation, OK432. Patients with malignant effusion of various origins were treated with intrapleural administration of OK432, and clinical responses were assessed by cytological and chest X-ray examinations. Pleural exudate cells (PEC), obtained before and after the administration of OK432 (designated as pre- and OK432-PEC, respectively), were subjected to TCR analysis. Both pre-PEC and OK432-PEC showed highly diverse expressions of TCRV beta gene usage in either type of PEC. The frequency of TCRV beta 20 gene expression in OK432-PEC was significantly higher than in pre-PEC. Moreover, the over-expression of the TCRV beta 20 gene usage was also induced in the peripheral blood lymphocytes and pre-PEC of patients by in vitro OK432 stimulation, but not in the PBL of one healthy volunteer. Single-strand conformational polymorphism (SSCP) analysis revealed the clonotypes of these TCRV beta 20 genes. Autologous tumor-specific killing activity could be detected in OK432-PEC and was significantly reduced by treatment with a TCRV beta 20-specific monoclonal antibody. These findings suggest that the rearrangement of TCRV beta 20 gene usage may be involved in the autologous tumor-specific action of malignant effusions in the treatment with OK432.
Miyahara
E
E
Department of Surgical Oncology, Hiroshima University, Japan.
Yamaguchi
Y
Y
Hihara
J
J
Noma
K
K
Toge
T
T
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015139:Blotting, Southern; D005260:Female; D019674:Genes, T-Cell Receptor beta / Q000235:genetics*; D006801:Humans; D007167:Immunotherapy; D007267:Injections; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010844:Picibanil / Q000008:administration & dosage / Q000627:therapeutic use*; D010994:Pleura / Q000502:physiology; D016066:Pleural Effusion, Malignant / Q000235:genetics / Q000628:therapy*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015347:RNA Probes; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
D000970:Antineoplastic Agents; D015347:RNA Probes; D010844:Picibanil