Exploration of the Combination of PLK1 Inhibition with Immunotherapy in Cancer Treatment
Exploration of the Combination of PLK1 Inhibition with Immunotherapy in Cancer Treatment
复制标题
DOI：
10.1155/2018/3979527
复制
发表时间：
2018-01-01
影响因子：
--
通讯作者：
Wang, Xiaosheng
中科院分区：
文献类型：
--
作者：
Li, Mengyuan;Liu, Zhixian;Wang, Xiaosheng
背景PLK1过表达是致癌的，并且与各种癌症的不良预后相关。然而，目前的PLK1抑制剂取得了有限的临床成功。另一方面，尽管免疫疗法在治疗许多难治性癌症方面显示出功效，但大量患者对此类疗法没有反应。PLK1抑制与免疫疗法相结合用于癌症治疗的潜力值得探索。方法.我们分析了33种不同癌症类型中PLK1表达与肿瘤免疫的相关性。此外，我们分析了PLK1抑制剂的药物敏感性与癌细胞系中肿瘤免疫的相关性。此外，我们还探讨了PLK1与肿瘤免疫之间显著相关性的机制。最后，我们通过实验验证了生物信息学分析的一些结果。结果PLK 1表达水平高的肿瘤倾向于具有较低的免疫活性，如HLA表达降低，B细胞、NK细胞和肿瘤浸润淋巴细胞浸润减少。另一方面，肿瘤免疫力的提高可能会增加癌细胞对PLK1抑制剂的敏感性。PLK1与肿瘤免疫相关的主要机制可能在于肿瘤细胞周期和p53通路的异常。结论.我们的研究结果表明，PLK1抑制和免疫治疗组合可以实现协同抗肿瘤功效。
Background. PLK1 overexpression is oncogenic and is associated with poor prognosis in various cancers. However, the current PLK1 inhibitors have achieved limited clinical successes. On the other hand, although immunotherapies are demonstrating efficacy in treating many refractory cancers, a substantial number of patients do not respond to such therapies. The potential of combining PLK1 inhibition with immunotherapy for cancer treatment is worthy of exploration. Methods. We analyzed the associations of PLK1 expression with tumor immunity in 33 different cancer types. Moreover, we analyzed the associations of the drug sensitivities of PLK1 inhibitors with tumor immunity in cancer cell lines. Furthermore, we explored the mechanism underlying the significant associations between PLK1 and tumor immunity. Finally, we experimentally verified some findings from bioinformatics analysis. Results. The cancers with higher PLK1 expression levels tended to have lower immune activities, such as lower HLA expression and decreased B cells, NK cells and tumor-infiltrating lymphocytes infiltration. On the other side, elevated tumor immunity likely increased the sensitivity of cancer cells to PLK1 inhibitors. The main mechanism underlying the associations between PLK1 and tumor immunity may lie in the aberrant cell cycle and p53 pathways in cancers. Conclusions. Our findings implicate that the PLK1 inhibition and immunotherapy combination may achieve a synergistic antitumor efficacy.