YIV-906 potentiated anti-PD1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironment
Abstract YIV-906 (PHY906) is a standardized botanical cancer drug candidate developed with a systems biology approach—inspired by a traditional Chinese herbal formulation, historically used to treat gastrointestinal symptoms including diarrhea, nausea and vomiting. In combination with chemotherapy a...
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Nature Portfolio
2021
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oai:doaj.org-article:ae2979734ecc4108a42ccbc05970d9012021-12-02T14:34:02ZYIV-906 potentiated anti-PD1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironment10.1038/s41598-021-91623-32045-2322https://doaj.org/article/ae2979734ecc4108a42ccbc05970d9012021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91623-3https://doaj.org/toc/2045-2322Abstract YIV-906 (PHY906) is a standardized botanical cancer drug candidate developed with a systems biology approach—inspired by a traditional Chinese herbal formulation, historically used to treat gastrointestinal symptoms including diarrhea, nausea and vomiting. In combination with chemotherapy and/or radiation therapy, preclinical and clinical results suggest that YIV-906 has the potential to prolong survival and improve quality of life for cancer patients. Here, we demonstrated that YIV-906 plus anti-PD1 could eradicate all Hepa 1–6 tumors in all tumor bearing mice. YIV-906 was found to have multiple mechanisms of action to enhance adaptive and innate immunity. In combination, YIV-906 reduced PD1 or counteracted PD-L1 induction caused by anti-PD1 which led to higher T-cell activation gene expression of the tumor. In addition, YIV-906 could reduce immune tolerance by modulating IDO activity and reducing monocytic MDSC of the tumor. The combination of anti-PD1 and YIV-906 generated acute inflammation in the tumor microenvironment with more M1-like macrophages. YIV-906 could potentiate the action of interferon gamma (IFNg) to increase M1-like macrophage polarization while inhibiting IL4 action to decrease M2 macrophage polarization. Flavonoids from YIV-906 were responsible for modulating IDO activity and potentiating IFNg action in M1-like macrophage polarization. In conclusion, YIV-906 could act as an immunomodulator and enhance the innate and adaptive immune response and potentiate anti-tumor activity for immunotherapies to treat cancer.Xiaochen YangWing LamZaoli JiangFulan GuanXue HanRong HuWei CaiWilliam ChengShwu-Huey LiuPeikwen ChengYuping CaiNicholas J. W. RattrayCaroline H. JohnsonLieping ChenYung-Chi ChengNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
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Medicine R Science Q Xiaochen Yang Wing Lam Zaoli Jiang Fulan Guan Xue Han Rong Hu Wei Cai William Cheng Shwu-Huey Liu Peikwen Cheng Yuping Cai Nicholas J. W. Rattray Caroline H. Johnson Lieping Chen Yung-Chi Cheng YIV-906 potentiated anti-PD1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironment |
| description |
Abstract YIV-906 (PHY906) is a standardized botanical cancer drug candidate developed with a systems biology approach—inspired by a traditional Chinese herbal formulation, historically used to treat gastrointestinal symptoms including diarrhea, nausea and vomiting. In combination with chemotherapy and/or radiation therapy, preclinical and clinical results suggest that YIV-906 has the potential to prolong survival and improve quality of life for cancer patients. Here, we demonstrated that YIV-906 plus anti-PD1 could eradicate all Hepa 1–6 tumors in all tumor bearing mice. YIV-906 was found to have multiple mechanisms of action to enhance adaptive and innate immunity. In combination, YIV-906 reduced PD1 or counteracted PD-L1 induction caused by anti-PD1 which led to higher T-cell activation gene expression of the tumor. In addition, YIV-906 could reduce immune tolerance by modulating IDO activity and reducing monocytic MDSC of the tumor. The combination of anti-PD1 and YIV-906 generated acute inflammation in the tumor microenvironment with more M1-like macrophages. YIV-906 could potentiate the action of interferon gamma (IFNg) to increase M1-like macrophage polarization while inhibiting IL4 action to decrease M2 macrophage polarization. Flavonoids from YIV-906 were responsible for modulating IDO activity and potentiating IFNg action in M1-like macrophage polarization. In conclusion, YIV-906 could act as an immunomodulator and enhance the innate and adaptive immune response and potentiate anti-tumor activity for immunotherapies to treat cancer. |
| format |
article |
| author |
Xiaochen Yang Wing Lam Zaoli Jiang Fulan Guan Xue Han Rong Hu Wei Cai William Cheng Shwu-Huey Liu Peikwen Cheng Yuping Cai Nicholas J. W. Rattray Caroline H. Johnson Lieping Chen Yung-Chi Cheng |
| author_facet |
Xiaochen Yang Wing Lam Zaoli Jiang Fulan Guan Xue Han Rong Hu Wei Cai William Cheng Shwu-Huey Liu Peikwen Cheng Yuping Cai Nicholas J. W. Rattray Caroline H. Johnson Lieping Chen Yung-Chi Cheng |
| author_sort |
Xiaochen Yang |
| title |
YIV-906 potentiated anti-PD1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironment |
| title_short |
YIV-906 potentiated anti-PD1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironment |
| title_full |
YIV-906 potentiated anti-PD1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironment |
| title_fullStr |
YIV-906 potentiated anti-PD1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironment |
| title_full_unstemmed |
YIV-906 potentiated anti-PD1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironment |
| title_sort |
yiv-906 potentiated anti-pd1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironment |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/ae2979734ecc4108a42ccbc05970d901 |
| work_keys_str_mv |
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