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雄激素剥夺和放疗后前列腺癌组织中的浸润免疫细胞。

Infiltrating immune cells in prostate cancer tissue after androgen deprivation and radiotherapy.

机构信息

Department of Urology, Faculty of Medicine and Health, 59566Örebro University, Örebro, Sweden.

Department of Environmental and Life Sciences/Biology, 101086Karlstad University, Karlstad, Sweden.

出版信息

Int J Immunopathol Pharmacol. 2023 Jan-Dec;37:3946320231158025. doi: 10.1177/03946320231158025.

Abstract

OBJECTIVES

Androgen deprivation therapy (ADT) has long been a cornerstone in treatment of advanced prostate cancer (PCa), and is known to improve the results of radiotherapy (RT) for high-risk disease. The purpose of our study was to use a multiplexed immunohistochemical (mIHC) approach to investigate the infiltration of immune cells in PCa tissue after eight weeks of ADT and/or RT with 10 Gy.

METHODS

From a cohort of 48 patients divided into two treatment arms, we obtained biopsies before and after treatment and used a mIHC method with multispectral imaging to analyze the infiltration of immune cells in tumor stroma and tumor epithelium, focusing on areas with high infiltration.

RESULTS

Tumor stroma showed a significantly higher infiltration of immune cells compared to tumor epithelium. The most prominent immune cells were CD20 B-lymphocytes, followed by CD68 macrophages, CD8 cytotoxic T-cells, FOXP3 regulatory T-cells (Tregs), and T-bet Th1-cells. Neoadjuvant ADT followed by RT significantly increased the infiltration of all five immune cells. Numbers of Th1-cells and Tregs significantly increased after single treatment with ADT or RT. In addition, ADT alone increased the number of cytotoxic T-cells and RT increased the number of B-cells.

CONCLUSIONS

Neoadjuvant ADT in combination with RT results in a higher inflammatory response compared to RT or ADT alone. The mIHC method may be a useful tool for investigating infiltrating immune cells in PCa biopsies to understand how immunotherapeutic approaches can be combined with current PCa therapies.

摘要

目的

去势治疗(ADT)长期以来一直是治疗晚期前列腺癌(PCa)的基石,已知它可改善高危疾病的放射治疗(RT)结果。我们的研究目的是使用多重免疫组化(mIHC)方法来研究 ADT 和/或 10Gy RT 治疗 8 周后 PCa 组织中免疫细胞的浸润。

方法

从分为两个治疗组的 48 例患者队列中,我们在治疗前后获得了活检,并使用具有多光谱成像的 mIHC 方法来分析肿瘤基质和肿瘤上皮中免疫细胞的浸润,重点关注高浸润区域。

结果

与肿瘤上皮相比,肿瘤基质显示出更高的免疫细胞浸润。最突出的免疫细胞是 CD20 B 淋巴细胞,其次是 CD68 巨噬细胞、CD8 细胞毒性 T 细胞、FOXP3 调节性 T 细胞(Tregs)和 T-bet Th1 细胞。新辅助 ADT 后行 RT 显著增加了所有五种免疫细胞的浸润。单独 ADT 或 RT 治疗后 Th1 细胞和 Tregs 的数量显著增加。此外,ADT 单独增加了细胞毒性 T 细胞的数量,而 RT 增加了 B 细胞的数量。

结论

与单独 RT 或 ADT 相比,新辅助 ADT 联合 RT 可引起更高的炎症反应。mIHC 方法可能是一种有用的工具,可用于研究 PCa 活检中的浸润免疫细胞,以了解如何将免疫治疗方法与当前的 PCa 治疗相结合。

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