Since its discovery, IL-1β has taken center stage as a key mediator of a very broad spectrum of diseases revolving around immuno-mediated and inflammatory events. Predictably, the pleiotropic nature of this cytokine in human pathology has led to the development of targeted therapeutics with multiple treatment indications in the clinic. Following the accumulated findings of IL-1β’s central modulatory role in the immune system and the implication of inflammatory pathways in cancer, the use of IL-1β antagonists was first proposed and then also pursued for oncology disorders. However, this approach has consistently relied on the perceived need of interfering with IL-1β synthesized and secreted by immune cells. Herein, we discuss the importance of IL-1β derived from cancer cells which impacts primary tumors, particularly metastatic lesions, separately from and in addition to its more recognized role in immune-mediated inflammatory events. To this end, we focus on the instrumental contribution of IL-1β in the establishment and progression of advanced prostate adenocarcinoma. Special emphasis is placed on the potential role that the standard-of-care treatment strategies for prostate cancer patients have in unleashing IL-1β expression and production at metastatic sites. We conclude by reviewing the therapeutics currently used for blocking IL-1β signaling and propose a rationale for their concomitant use with standard-of-care treatments to improve the clinical outcomes of advanced prostate cancer.
自发现以来，IL-1β作为免疫介导和炎症事件相关疾病谱系的关键介质，始终占据核心地位。可以预见的是，该细胞因子在人类病理学中的多效性特征，推动了靶向治疗药物的研发，并在临床上获得多种治疗适应症。随着IL-1β在免疫系统中的核心调节作用及炎症通路与癌症关联性的证据积累，IL-1β拮抗剂首先被提出并随后应用于肿瘤疾病治疗。然而，这一策略始终基于干扰免疫细胞合成与分泌IL-1β的传统认知。本文重点探讨癌细胞来源的IL-1β对原发性肿瘤（特别是转移病灶）的重要影响，这一独立于免疫介导炎症事件的作用机制尚未得到充分重视。为此，我们聚焦IL-1β在晚期前列腺腺癌发生发展中的关键作用，特别强调当前前列腺癌标准治疗方案可能促进转移灶IL-1β表达与产生的潜在机制。最后，通过评述现有阻断IL-1β信号通路的治疗策略，我们提出将其与标准治疗方案联用以改善晚期前列腺癌临床结局的理论依据。
肿瘤(癌症)患者之家