【文献速递】-Prostate cancer hijacks t

Prostate cancer is difficult to treat because of molecular, cellular and clinical heterogeneity. Using single-cell RNA sequencing, a recent study reveals unexpected transcriptomic reprograming in immune cells and non-immune components of the tumour microenvironment, which may lead to viable therapeutic approaches against prostate cancer.
Despite a declining death rate over the last 30 years thanks to the advent of new treatment regimens, prostate cancer (PCa) remains the most dominant male malignancy in the world. At the initial diagnosis, PCa can be clinically localised (77%), extended to pelvic lymph nodes (11%), or found to have been metastatic (6%). The five-year survival rate for localised PCa is almost 100%, but for metastatic prostate cancer (mPCa) this drops to only 31%1. Although mPCa is initially responsive to inhibition of androgen receptor (AR) signalling and many men benefit from years of cancer control, others manifest rapid resistance. These resistant forms of mPCa lack standard-of-care therapy and have developed through heterogeneous mechanisms. They may also become AR null or undergo lineage plasticity (that is, the ability of cells to transition from one committed pathway to another), resulting in a mean survival rate of 12 months2. Therefore, to meet this clinical need and provide effective treatment opportunities for these patients, it is paramount to study cancer heterogeneity and clonal diversity alongside the development and impact of the tumour microenvironment (TME), which includes blood vessels, immune cells, fibroblasts and the extracellular matrix (ECM). In this issue of Nature Cell Biology, Chen et al.3 utilised single-cell transcriptomic analysis of 24 PCa samples to study intracellular heterogeneity and TME factors, such as tumour-infiltrating immune components. By including primary PCa, lymph node metastases, as well as non-cancerous prostate tissue, the authors made some unexpected observations regarding the TME.

前列腺癌由于分子、细胞和临床的异质性而难以治疗。利用单细胞RNA测序，最近的一项研究揭示了在免疫细胞和肿瘤微环境的非免疫成分中意外的转录组重编程，这可能导致对前列腺癌可行的治疗方法。
尽管在过去的30年里，由于新治疗方案的出现，前列腺癌的死亡率有所下降，但它仍然是世界上最主要的男性恶性肿瘤。在最初诊断时，前列腺癌可以被临床定位(77%)，扩展到盆腔淋巴结(11%)，或发现转移(6%)。局部前列腺癌的5年生存率几乎为100%，但转移性前列腺癌的5年生存率仅为31%1。尽管mPCa最初对雄激素受体(AR)信号的抑制有反应，并且许多男性受益于多年的癌症控制，但其他人表现出快速的耐药性。这些耐药形式的mPCa缺乏标准治疗，并通过异质机制发展。它们也可能成为无AR或经历谱系可塑性(即细胞从一种承诺通路过渡到另一种通路的能力)，导致平均生存率为12个月2。因此，为了满足这一临床需求并为这些患者提供有效的治疗机会，研究肿瘤的异质性和克隆多样性以及肿瘤微环境(TME)的发展和影响至关重要，TME包括血管、免疫细胞、成纤维细胞和细胞外基质(ECM)。在本期《自然细胞生物学》中，Chen等人利用24个PCa样本的单细胞转录组分析来研究细胞内异质性和TME因素，如肿瘤浸润免疫成分。通过包括原发性前列腺癌，淋巴结转移，以及非癌性前列腺组织，作者对TME做了一些意想不到的观察。