复发性新辅助单纯疱疹病毒联合更昔洛韦基因治疗前列腺癌的细胞病变效应和局部免疫反应

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

作者信息

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

机构信息

Department of Pathology, St. Marianna University School of Medicine Yokohama-City Seibu Hospital, Yokohama, Kanagawa, Japan.

Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.

出版信息

Asian J Urol. 2021 Jul;8(3):280-288. doi: 10.1016/j.ajur.2020.06.004. Epub 2020 Jun 16.

DOI:10.1016/j.ajur.2020.06.004

PMID:34401335

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8356062/

Abstract

OBJECTIVE

Cytopathic effects and local immune response were analyzed histologically in prostatic cancer (PCa) with herpes simplex virus-thymidine kinase (HSV-)/ganciclovir (GCV) gene therapy (GT).

METHODS

Four high-risk PCa patients who received HSV-/GCV GT were investigated. After two cycles of intraprostatic injection of HSV- and administration of GCV, radical prostatectomy was performed. Formalin-fixed, paraffin-embedded sections were evaluated using immunohistochemistry. PCa with hormone therapy (HT, =3) or without neoadjuvant therapy (NT, =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, <0.0001) as well as CD4+ T cells and CD20+ B cells (ρ=0.644, <0.0001) in PCa with GT.

CONCLUSIONS

Enhanced cytopathic effect and local immune response might be indicated in PCa patients with HSV-/GCV gene therapy.

摘要

目的

通过组织学方法分析单纯疱疹病毒胸苷激酶（HSV-）/更昔洛韦（GCV）基因治疗（GT）对前列腺癌（PCa）的细胞病变效应和局部免疫反应。

方法

对4例接受HSV-/GCV GT治疗的高危PCa患者进行研究。在前列腺内注射HSV-并给予GCV两个周期后，进行根治性前列腺切除术。使用免疫组织化学方法评估福尔马林固定、石蜡包埋的切片。还检查了风险相当的接受激素治疗（HT，n = 3）或未接受新辅助治疗（NT，n = 4）的PCa作为对照。在癌组织的至少三个区域中对免疫反应阳性细胞进行计数。计算标记指数（LI）作为百分比值。

结果

与活检相比，GT组的单链DNA LI增加，表明细胞凋亡，以及肿瘤浸润淋巴细胞和CD68阳性巨噬细胞增加。GT组病例的单链DNA（ssDNA）LI、CD4/CD8阳性T细胞和CD68阳性巨噬细胞（包括M1/M2巨噬细胞）数量明显高于HT组或NT组病例。然而，不同类型病例之间CD20阳性B细胞无显著差异。在接受GT治疗的PCa中，CD8 + T细胞与CD68 +巨噬细胞之间（ρ = 0.656，P < 0.0001）以及CD4 + T细胞与CD20 + B细胞之间（ρ = 0.644，P < 0.0001）存在强相关性。