Cytopathic effects and local immune responses in repeated neoadjuvant HSV- tk + ganciclovir gene therapy for prostate cancer

摘要

ObjectiveCytopathic effects and local immune response were analyzed histologically in prostatic cancer (PCa) within situherpes simplex virus-thymidine kinase (HSV-tk)/ganciclovir (GCV) gene therapy (GT).MethodsFour high-risk PCa patients who received HSV-tk/GCV GT were investigated. After two cycles of intraprostatic injection of HSV-tkand administration of GCV, radical prostatectomy was performed. Formalin-fixed, paraffin-embedded sections were evaluated using immunohistochemistry. PCa with hormone therapy (HT,n=3) or without neoadjuvant therapy (NT,n=4) that were equivalent in terms of risk were also examined as reference. Immunoreactively-positive cells were counted in at least three areas in cancer tissue. Labeling indices (LI) were calculated as percentage values.ResultsssDNA LI in GT increased, indicating apoptosis, as well as tumor-infiltrating lymphocytes and CD68-positive macrophages, compared with their biopsies. GT cases showed significantly higher numbers of single-stranded DNA (ssDNA) LI, CD4/CD8-positive T cells and CD68-positive macrophages including M1/M2 macrophages than HT or NT cases. However, there was no significant difference in CD20-positive B cells among the types of case. There were strong correlations between CD8+ T cells and CD68+ macrophages (ρ=0.656,p<0.0001) as well as CD4+ T cells and CD20+ B cells (ρ=0.644,p<0.0001) in PCa with GT.ConclusionsEnhanced cytopathic effect and local immune response might be indicated in PCa patients with HSV-tk/GCV gene therapy.