Despite recent advances in cancer immunotherapy, the efficacy of these therapies for the treatment of human prostate cancer patients is low due to the complex immune evasion mechanisms (IEMs) of prostate cancer and the lack of predictive biomarkers for patient responses. To understand the IEMs in prostate cancer and apply such understanding to the design of personalized immunotherapies, we analyzed the RNA-seq data for prostate adenocarcinoma from The Cancer Genome Atlas (TCGA) using a combination of biclustering, differential expression analysis, immune cell typing, and machine learning methods. The integrative analysis identified eight clusters with different IEM combinations and predictive biomarkers for each immune evasion cluster. Prostate tumors employ different combinations of IEMs. The majority of prostate cancer patients were identified with immunological ignorance (89.8%), upregulated cytotoxic T lymphocyte-associated protein 4 (CTLA4) (58.8%), and upregulated decoy receptor 3 (DcR3) (51.6%). Among patients with immunologic ignorance, 41.4% displayed upregulated DcR3 expression, 43.26% had upregulated CTLA4, and 11.4% had a combination of all three mechanisms. Since upregulated programmed cell death 1 (PD-1) and/or CTLA4 often co-occur with other IEMs, these results provide a plausible explanation for the failure of immune checkpoint inhibitor monotherapy for prostate cancer. These findings indicate that human prostate cancer specimens are mostly immunologically cold tumors that do not respond well to mono-immunotherapy. With such identified biomarkers, more precise treatment strategies can be developed to improve therapeutic efficacy through a greater understanding of a patient’s immune evasion mechanisms.

中文翻译：

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人类前列腺癌的免疫状况：免疫逃逸机制和个性化免疫疗法的生物标志物。

尽管在癌症免疫疗法方面有最新进展，但由于前列腺癌的复杂免疫逃逸机制（IEM）和缺乏用于患者反应的预测性生物标志物，这些疗法在治疗人类前列腺癌患者中的功效仍然很低。为了了解前列腺癌中的IEM并将这种理解应用于个性化免疫疗法的设计，我们结合了双聚类分析，差异表达分析，免疫细胞分型等方法，分析了The Cancer Genome Atlas（TCGA）的前列腺腺癌RNA-seq数据，和机器学习方法。综合分析确定了八个簇，每个免疫逃逸簇具有不同的IEM组合和预测性生物标志物。前列腺肿瘤采用IEM的不同组合。多数前列腺癌患者被鉴定为免疫学无知（89.8％），细胞毒性T淋巴细胞相关蛋白4（CTLA4）上调（58.8％）和诱饵受体3（DcR3）上调（51.6％）。在免疫性无知的患者中，有41.4％的患者显示DcR3表达上调，43.26％的患者CTLA4升高，11.4％的患者综合了这三种机制。由于上调的程序性细胞死亡1（PD-1）和/或CTLA4通常与其他IEM并发，因此这些结果为免疫检查点抑制剂单一疗法对前列腺癌治疗失败提供了合理的解释。这些发现表明，人类前列腺癌标本大多是免疫性较冷的肿瘤，对单一免疫疗法的反应不佳。有了这些确定的生物标记，