Comprehensive transcriptome profiling in elderly cancer patients reveals aging-altered immune cells and immune checkpoints
Comprehensive transcriptome profiling in elderly cancer patients reveals aging-altered immune cells and immune checkpoints
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老年癌症患者的全面转录组分析揭示了衰老改变的免疫细胞和免疫检查点
DOI：
10.1002/ijc.31875
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发表时间：
2019
影响因子：
6.4
通讯作者：
Fan Yihui
中科院分区：
文献类型：
--
作者：
Wu Yingcheng;Wei Jinhuan;Chen Xia;Qin Yongwei;Mao Renfang;Song Jian;Fan Yihui
衰老是癌症发展的唯一最重要的风险因素。然而，衰老对癌症微环境的潜在影响仍然知之甚少。在这里，我们进行了泛癌症转录组分析，以确定18种癌症类型的衰老特异性分子模式。引人注目的是，衰老特异性分子特征将人类癌症分为两种类型，包括强和弱衰老效应组。在16种癌症类型（强衰老效应组）中观察到显著的衰老相关分子特征，如乳腺浸润性癌和急性髓性白血病。在这16种癌症类型中，与年轻患者相比，老年患者的生存率明显较差，但在弱老化效应癌症中没有发现这种观察结果。与衰老相关的癌症相关分子在23条通路中显著富集，包括EMT和KRAS信号传导。更有趣的是，在癌症微环境中，衰老显著抑制了适应性免疫，但引人注目的是，增加了浸润的先天免疫细胞的数量。进一步分析表明，包括PD-1、PD-L1、PD-L2和CTLA-4在内的免疫检查点的表达主要与年龄相关。一般来说，老年患者的癌细胞表现出更具侵袭性的表型，与年轻患者相比，其周围的微环境处于更强的免疫抑制状态。我们的研究提供了泛癌症中衰老相关分子特征的系统性理解，并表明在大多数癌症类型中开发衰老特异性治疗策略的临床要求。此外，衰老改变的免疫细胞和免疫检查点应在癌症免疫治疗中考虑。
Aging is the single most significant risk factor for cancer development. However, the potential impact of aging on cancer microenvironment remains poorly understood. Here, we performed a pan‐cancer transcriptome analysis to identify aging‐specific molecular patterns across 18 cancer types. Strikingly, aging‐specific molecular features define human cancers into two types, including the strong and weak aging‐effect groups. Significant aging associated molecular signature was observed in 16 cancer types (strong aging‐effect group) such as breast invasive carcinoma and acute myeloid leukemia. In such 16 cancer types, old patients showed obvious poor survival compared to young patients, but this observation was not found in the weak aging‐effect cancers. Aging‐associated cancer‐relevant molecules significantly enriched in 23 pathways including EMT and KRAS signaling. More interestingly, in cancer microenvironment, aging significantly restrains adaptive immunity, but strikingly, increases the number of infiltrated innate immune cells. Further analysis shows that the expression of immune checkpoints including PD‐1, PD‐L1, PD‐L2 and CTLA‐4 are mostly correlated with age. In general, cancer cells in elderly patients show a more aggressive phenotype and their surrounding microenvironment is under a more immune suppression status compared to young patients. Our study provides a systematic understanding of aging‐associated molecular features in pan‐cancer and indicates a clinical requirement to develop aging‐specific therapeutic strategies in a majority of cancer types. Furthermore, aging‐altered immune cells and immune checkpoints should be considered in cancer immunotherapy.