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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-91623-3 |
| _version_ | 1818835399421722624 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T02:50:06Z |
| format | Article |
| id | doaj.art-ae2979734ecc4108a42ccbc05970d901 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T02:50:06Z |
| publishDate | 2021-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ae2979734ecc4108a42ccbc05970d9012022-12-21T20:38:41ZengNature PortfolioScientific Reports2045-23222021-06-0111111210.1038/s41598-021-91623-3YIV-906 potentiated anti-PD1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironmentXiaochen Yang0Wing Lam1Zaoli Jiang2Fulan Guan3Xue Han4Rong Hu5Wei Cai6William Cheng7Shwu-Huey Liu8Peikwen Cheng9Yuping Cai10Nicholas J. W. Rattray11Caroline H. Johnson12Lieping Chen13Yung-Chi Cheng14Department of Pharmacology, Yale University School of MedicineDepartment of Pharmacology, Yale University School of MedicineDepartment of Pharmacology, Yale University School of MedicineDepartment of Pharmacology, Yale University School of MedicineDepartment of Immunobiology, Yale University School of MedicineDepartment of Pharmacology, Yale University School of MedicineDepartment of Pharmacology, Yale University School of MedicineYiviva, IncYiviva, IncYiviva, IncEnvironmental Health Sciences, Yale University School of Public HealthEnvironmental Health Sciences, Yale University School of Public HealthEnvironmental Health Sciences, Yale University School of Public HealthDepartment of Immunobiology, Yale University School of MedicineDepartment of Pharmacology, Yale University School of MedicineAbstract 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.https://doi.org/10.1038/s41598-021-91623-3 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-91623-3 |
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