Department of Urology, Faculty of Medicine and Health, 59566Örebro University, Örebro, Sweden.
Department of Environmental and Life Sciences/Biology, 101086Karlstad University, Karlstad, Sweden.
Int J Immunopathol Pharmacol. 2023 Jan-Dec;37:3946320231158025. doi: 10.1177/03946320231158025.
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.
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.
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.
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.
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。
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。
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。
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。
