Department of Clinical Medicine, Graduate School, Zhejiang Chinese Medical University, Hangzhou, China.
Department of Gastroenterology, Wenzhou People's Hospital, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, China.
Front Immunol. 2021 Apr 19;12:664847. doi: 10.3389/fimmu.2021.664847. eCollection 2021.
Lysine (K)-specific demethylase 5C () plays a significant role in the tumor cell proliferation, invasion, drug resistance and the regulation of tumor-related gene expression. Here, we aimed to investigate its predictive value in patients with cancers received immune checkpoint inhibitors (ICIs). We explored the predictive value of alterations and the association between alteration and immune landscape by using published cohort with clinical outcome and sequenced data from online database. The frequency of alterations was 2.1% across 48045 tumor samples with different cancers from 185 studies. alterations were correlated with markedly inferior overall survival (OS, 53 vs. 102 months, <0.0001) than those without. However, in ICI-treated group, patients with alterations had a substantially prolonged OS than the wild-type group (not reached vs. 18 months, =0.0041). The predictive value of alterations for ICI treatment outcome was not observed in patients with microsatellite-stable tumors (=0.2875). Intriguingly, patients with non-small-cell lung cancer and alterations receiving ICI had the better progression-free survival than wild type group (13.2 vs. 3.2 months, =0.0762). Mechanistically, altered tumors had dramatically higher TMB level and was associated with significantly higher level of CD8+ T cell infiltration and T effector signature. In conclusion, alterations was correlated with enhanced tumor immunogenicity and inflamed anti-tumor immunity, thus resulting in better treatment outcome in cancer patients receiving ICIs.
赖氨酸（K）特异性去甲基酶 5C（）在肿瘤细胞增殖、侵袭、耐药以及肿瘤相关基因表达调控中发挥着重要作用。在这里，我们旨在研究其在接受免疫检查点抑制剂（ICIs）治疗的癌症患者中的预测价值。我们通过使用具有临床结局的已发表队列和在线数据库中的测序数据，探索了 改变的预测价值以及 改变与免疫景观之间的关联。在来自 185 项研究的 48045 个不同癌症的肿瘤样本中，改变的频率为 2.1%。与无改变的患者相比，改变的患者总体生存率（OS，53 与 102 个月，<0.0001）明显更差。然而，在接受 ICI 治疗的组中，改变的患者的 OS 明显长于野生型组（未达到与 18 个月，=0.0041）。在微卫星稳定的肿瘤患者中（=0.2875），未观察到 改变对 ICI 治疗结局的预测价值。有趣的是，接受 ICI 治疗的非小细胞肺癌和 改变的患者的无进展生存期优于野生型组（13.2 与 3.2 个月，=0.0762）。从机制上讲，改变的肿瘤具有更高的 TMB 水平，并与更高水平的 CD8+T 细胞浸润和 T 效应子特征相关。总之，改变与增强的肿瘤免疫原性和炎症性抗肿瘤免疫有关，从而导致接受 ICI 治疗的癌症患者的治疗效果更好。
