关注雄激素受体（AR）在推动前列腺癌（PCa）上皮细胞生长方面的中心转录因子作用已经越来越高。然而，我们对雄激素在PCa浸润免疫细胞中的作用以及雄激素剥夺治疗（ADT）——治疗晚期PCa的一线治疗方法，对PCa免疫微环境的影响的理解仍然有限。另一方面，免疫检查点阻断已经彻底改变了某些癌症类型的治疗方法，但由于免疫抑制环境，它在晚期PCa患者中没有任何益处。本研究报告显示，AR信号通路在PCa的肿瘤相关巨噬细胞（TAM）中被明显激活。AR在TAM中作为IL1B的转录抑制因子。ADT释放了AR对IL1B的抑制，从而导致TAM中IL-1β的过度表达和分泌。IL-1β诱导髓状造血源性抑制细胞（MDSCs）积聚，抑制细胞毒性T细胞的激活，从而导致免疫抑制的微环境。重要的是，联合ADT和免疫检查点抑制剂抗IL-1β抗体和抗PD-1抗体能够更强地对阉割后的PCa产生抗癌作用。因此，IL-1β是治疗晚期PCa的重要雄激素响应性免疫治疗靶点。©2023 Wiley-VCH GmbH出版的Advanced Science。

Great attention is paid to the role of androgen receptor (AR) as a central transcriptional factor in driving the growth of prostate cancer (PCa) epithelial cells. However, the understanding of the role of androgen in PCa-infiltrated immune cells and the impact of androgen deprivation therapy (ADT), the first-line treatment for advanced PCa, on the PCa immune microenvironment remains limited. On the other hand, immune checkpoint blockade has revolutionized the treatment of certain cancer types, but fails to achieve any benefit in advanced PCa, due to an immune suppressive environment. In this study, it is reported that AR signaling pathway is evidently activated in tumor-associated macrophages (TAMs) of PCa both in mice and humans. AR acts as a transcriptional repressor for IL1B in TAMs. ADT releases the restraint of AR on IL1B and therefore leads to an excessive expression and secretion of IL-1β in TAMs. IL-1β induces myeloid-derived suppressor cells (MDSCs) accumulation that inhibits the activation of cytotoxic T cells, leading to the immune suppressive microenvironment. Critically, anti-IL-1β antibody coupled with ADT and the immune checkpoint inhibitor anti-PD-1 antibody exerts a stronger anticancer effect on PCa following castration. Together, IL-1β is an important androgen-responsive immunotherapeutic target for advanced PCa.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.