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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\u2009=\u200965.31%) are validated by multiple evidence, including published experimental data from clinical studies, in vitro and\n                    <jats:italic>in vivo<\/jats:italic>\n                    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\n                    <jats:italic>Huangqin<\/jats:italic>\n                    (\n                    <jats:italic>Scutellaria baicalensis Georgi<\/jats:italic>\n                    ) 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.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-82857-2","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T16:23:28Z","timestamp":1612801408000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["In silico identification of natural products from Traditional Chinese Medicine for cancer immunotherapy"],"prefix":"10.1038","volume":"11","author":[{"given":"Chuipu","family":"Cai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghai","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiude","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiansong","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,8]]},"reference":[{"key":"82857_CR1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","volume":"68","author":"F Bray","year":"2018","unstructured":"Bray, F. et al. 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