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

Nobuyuki Yanagisawa, Takefumi Satoh, Ken ichi Tabata, Hideyasu Tsumura, Yasutomo Nasu, Masami Watanabe, Timothy C. Thompson, Isao Okayasu, Yoshiki Murakumo, Shiro Baba, Masatsugu Iwamura

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Cytopathic effects and local immune response were analyzed histologically in prostatic cancer (PCa) with in situ herpes simplex virus-thymidine kinase (HSV-tk)/ganciclovir (GCV) gene therapy (GT). Methods: Four high-risk PCa patients who received HSV-tk/GCV GT were investigated. After two cycles of intraprostatic injection of HSV-tk and 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. Results: ssDNA 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. Conclusions: Enhanced cytopathic effect and local immune response might be indicated in PCa patients with HSV-tk/GCV gene therapy.

Original languageEnglish
Pages (from-to)280-288
Number of pages9
JournalAsian Journal of Urology
Volume8
Issue number3
DOIs
Publication statusPublished - Jul 2021

Keywords

  • Ganciclovir
  • HSV-tk
  • Immunohistochemistry
  • Prostate carcinoma
  • Suicide gene therapy

ASJC Scopus subject areas

  • Urology

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