Department of Computer Science, Key Laboratory of Intelligent Manufacturing Technology of Ministry of Education, Shantou University, Shantou, 515000, China.
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
Sci Rep. 2021 Feb 8;11(1):3332. doi: 10.1038/s41598-021-82857-2.
Advances in immunotherapy have revolutionized treatments in many types of cancer. Traditional Chinese Medicine (TCM), which has a long history of clinical adjuvant application against cancer, is emerging as an important medical resource for developing innovative cancer treatments, including immunotherapy. In this study, we developed a quantitative and systems pharmacology-based framework to identify TCM-derived natural products for cancer immunotherapy. Specifically, we integrated 381 cancer immune response-related genes and a compound-target interaction network connecting 3273 proteins and 766 natural products from 66 cancer-related herbs based on literature-mining. Via systems pharmacology-based prediction, we uncovered 182 TCM-derived natural products having potential anti-tumor immune responses effect. Importantly, 32 of the 49 most promising natural products (success rate = 65.31%) are validated by multiple evidence, including published experimental data from clinical studies, in vitro and in vivo assays. We further identified the mechanism-of-action of TCM in cancer immunotherapy using network-based functional enrichment analysis. We showcased that three typical natural products (baicalin, wogonin, and oroxylin A) in Huangqin (Scutellaria baicalensis Georgi) potentially overcome resistance of known oncology agents by regulating tumor immunosuppressive microenvironments. In summary, this study offers a novel and effective systems pharmacology infrastructure for potential cancer immunotherapeutic development by exploiting the medical wealth of natural products in TCM.
免疫疗法的进步已经彻底改变了许多类型癌症的治疗方法。传统中药（TCM）在癌症的临床辅助应用方面有着悠久的历史，它正在成为开发创新癌症治疗方法（包括免疫疗法）的重要医学资源。在这项研究中，我们开发了一种基于定量和系统药理学的框架，用于识别用于癌症免疫疗法的中药衍生天然产物。具体来说，我们整合了 381 个癌症免疫反应相关基因，以及一个化合物-靶标相互作用网络，该网络连接了 66 种癌症相关草药中的 3273 种蛋白质和 766 种天然产物，基于文献挖掘。通过基于系统药理学的预测，我们发现了 182 种具有潜在抗肿瘤免疫反应作用的中药衍生天然产物。重要的是，在 49 种最有希望的天然产物中，有 32 种（成功率=65.31%）得到了多个证据的验证，包括来自临床研究、体外和体内试验的已发表实验数据。我们还使用基于网络的功能富集分析来确定 TCM 在癌症免疫疗法中的作用机制。我们展示了黄芩（Scutellaria baicalensis Georgi）中的三种典型天然产物（黄芩苷、汉黄芩素和氧化苦参碱）可能通过调节肿瘤免疫抑制微环境来克服已知肿瘤药物的耐药性。总之，这项研究通过利用 TCM 中天然产物的医学财富，为潜在的癌症免疫治疗开发提供了一种新颖有效的系统药理学基础设施。
