Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
Integrated Biomedical Sciences Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
Asian J Androl. 2023 Mar-Apr;25(2):171-178. doi: 10.4103/aja202283.
Although immunotherapy has revolutionized cancer treatment and achieved remarkable success across many different cancer types, only a subset of patients shows meaningful clinical responses. In particular, advanced prostate cancer exhibits overwhelming de novo resistance to immune checkpoint blockade therapy. This is primarily due to the immunosuppressive tumor microenvironment of prostate cancer. Therefore, it is paramount to understand how prostate cancer cell-intrinsic mechanisms promote immune evasion and foster an immunosuppressive microenvironment. Here, we review recent findings that reveal the roles of the genetic alterations, androgen receptor signaling, cancer cell plasticity, and oncogenic pathways in shaping the immunosuppressive microenvironment and thereby driving immunotherapy resistance. Based on preclinical and clinical observations, a variety of therapeutic strategies are being developed that may illuminate new paths to enhance immunotherapy efficacy in prostate cancer.
尽管免疫疗法已经彻底改变了癌症治疗方式，并在许多不同类型的癌症中取得了显著的成功，但只有一部分患者表现出有意义的临床反应。特别是，晚期前列腺癌对免疫检查点阻断治疗表现出压倒性的新出现的耐药性。这主要是由于前列腺癌的免疫抑制肿瘤微环境。因此，了解前列腺癌细胞内在机制如何促进免疫逃逸并培育免疫抑制微环境至关重要。在这里，我们回顾了最近的发现，这些发现揭示了遗传改变、雄激素受体信号、癌细胞可塑性和致癌途径在塑造免疫抑制微环境从而驱动免疫治疗耐药性方面的作用。基于临床前和临床观察，正在开发各种治疗策略，这些策略可能为提高前列腺癌免疫治疗效果开辟新途径。
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