Androgen deprivation therapy (ADT) is a cornerstone treatment for locally advanced or metastatic prostate cancer (PCa). However, its potential effects on the tumor immune microenvironment (TIM) of PCa patients and the underlying mechanism remain largely unclear. To explore the effects of ADT on PCa TIM, RNA sequencing was performed on six paired pre-ADT biopsy and post-ADT PCa lesions, and five paired paracancerous benign tissues from patients receiving neoadjuvant ADT with locally advanced PCa. Bioinformatics methods including ESTIMATE and ssGSEA were used to evaluate the stromal immune score and immune cell infiltration in PCa and paracancerous tissues. Weighted correlation network analysis was used to screen hub genes in the ADT-induced immune remodeling process. The results showed differences exist between PCa and paracancerous tissues in response to ADT. Compared with paracancerous tissues, the immune remodeling effect of ADT in PCa was more intense. ZFP36, JUNB, and SOCS3 served as hub genes in the ADT-induced immune remodeling process and were associated with PSA recurrent-free survival in the TCGA and our neoadjuvant ADT cohort. To investigate the joint action of the above three hub genes, an immune signature score was constructed. The results showed that immune signature score-based immune subtypes reveal the heterogeneity of the immune microenvironment of PCa and showed significant differences in patient prognosis, tumor immune infiltration, mutation burden, and landscape.

雄激素剥夺疗法 (ADT) 是局部晚期或转移性前列腺癌 (PCa) 的基石疗法。然而，其对 PCa 患者肿瘤免疫微环境 (TIM) 的潜在影响及其潜在机制尚不清楚。为了探索 ADT 对 PCa TIM 的影响，对来自接受新辅助 ADT 和局部晚期 PCa 的患者的六对 ADT 前活检和 ADT 后 PCa 病变以及五对癌旁良性组织进行了 RNA 测序。包括 ESTIMATE 和 ssGSEA 在内的生物信息学方法用于评估 PCa 和癌旁组织中的基质免疫评分和免疫细胞浸润。加权相关网络分析用于筛选 ADT 诱导的免疫重塑过程中的枢纽基因。结果表明，PCa 和癌旁组织对 ADT 的反应存在差异。与癌旁组织相比，ADT对PCa的免疫重构作用更为强烈。ZFP36、JUNB和SOCS3在 ADT 诱导的免疫重塑过程中充当中心基因，并且与 TCGA 和我们的新辅助 ADT 队列中的 PSA 无复发生存相关。为了研究上述三个枢纽基因的联合作用，构建了免疫特征评分。结果表明，基于免疫特征评分的免疫亚型揭示了 PCa 免疫微环境的异质性，并在患者预后、肿瘤免疫浸润、突变负荷和景观方面表现出显着差异。