Prostate cancer (PCa) is the most frequently diagnosed cancer for men in the U.S. but does not impede patient survival until the disease is metastatic. Metastatic lesions most frequently occur in the bone, which exhibits a distinct microenvironment of immune and bone cell populations. Advances in the diagnosis and treatment of primary PCa allow for the use of tailored therapeutic approaches based on biomarkers, protein expression, and histopathology. Understanding the molecular and cellular characteristics of primary tumors has advanced therapeutic development and survival for patients with PCa. Personalized medicine has only recently emerged for the treatment of metastatic bone lesions. Tumor induced bone disease (TIBD) in patients with PCa can be classified into lytic, blastic, or mixed pathologies, with most patients exhibiting the blastic phenotype. Progress has been made in treating TIBD, but metastatic PCa has yet to be cured. Immune checkpoint inhibitors have exhibited limited responses in immunosuppressive PCa tumors, but have yet to be assessed in metastatic sites which may be susceptible to an increased inflammatory response. Recent discoveries have uncovered distinct tumor microenvironments (TMEs) of blastic and lytic bone metastases from patients with PCa, identifying actionable targets for therapeutic applications, including immune checkpoint inhibitors and targeted therapeutics. Enrichment for macrophages and T cells in patient samples suggests metastatic sites may be reappraised as immunologically targetable, despite their immunologically “cold” primary tumors. The practice of performing bone biopsies will help identify unique cellular and protein targets in the bone TME that can guide therapy decisions.

中文翻译：

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整合前列腺癌的免疫微环境诱发的骨病。

前列腺癌（PCa）是美国男性中最常被诊断出的癌症，但是在该疾病转移之前，它不会妨碍患者的生存。转移性病变最常发生在骨骼中，表现出独特的免疫和骨骼细胞群体微环境。在原发性PCa的诊断和治疗方面的进步允许使用基于生物标记，蛋白质表达和组织病理学的量身定制的治疗方法。了解原发性肿瘤的分子和细胞特征对于PCa患者具有先进的治疗发展和生存率。个性化药物只是最近才出现，用于治疗转移性骨病变。PCa患者的肿瘤性骨病（TIBD）可以分为溶解性，成骨性或混合性病理，大多数患者表现出弹力表型。在治疗TIBD方面已取得进展，但转移性PCa尚未治愈。免疫检查点抑制剂在免疫抑制性PCa肿瘤中显示出有限的反应，但尚未在可能易受炎症反应增加的转移部位进行评估。最近的发现发现了PCa患者的独特的肿瘤微环境（TME）的弹塑性和溶解性骨转移，确定了可治疗的治疗靶标，包括免疫检查点抑制剂和靶向治疗剂。患者样品中巨噬细胞和T细胞的富集提示，尽管转移部位具有免疫“冷”原发性肿瘤，但仍可重新评估为具有免疫学靶向性。