Synergistic inhibition of pancreatic cancer with anti-PD-L1 and c-Myc inhibitor JQ1
Human pancreatic ductal adenocarcinoma (PDAC) exhibits marginal responses to anti-PD-1/PD-L1 immunotherapy and its mechanism remains poorly understood. We have investigated the effect of anti-PD-L1 and c-Myc inhibition in PDAC. Using 87 patients with PDAC from our hospital database we found a signif...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-05-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2019.1581529 |
| _version_ | 1818331696444997632 |
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| author | Yu Pan Qinglin Fei Ping Xiong Jianyang Yang Zheyang Zhang Xianchao Lin Minggui Pan Fengchun Lu Heguang Huang |
| author_facet | Yu Pan Qinglin Fei Ping Xiong Jianyang Yang Zheyang Zhang Xianchao Lin Minggui Pan Fengchun Lu Heguang Huang |
| author_sort | Yu Pan |
| collection | DOAJ |
| description | Human pancreatic ductal adenocarcinoma (PDAC) exhibits marginal responses to anti-PD-1/PD-L1 immunotherapy and its mechanism remains poorly understood. We have investigated the effect of anti-PD-L1 and c-Myc inhibition in PDAC. Using 87 patients with PDAC from our hospital database we found a significant correlation between the expression of PD-L1 and c-Myc. Moreover, the expression of both PD-L1 and c-Myc was associated with poor overall survival. In addition, we confirmed this finding with the PDAC patients in the TCGA database. Using several PDAC cell lines we demonstrated a significant correlation between the expression of PD-L1 and c-Myc. We also found that expression of PD-L1 correlated with high-grade histology. JQ1, an inhibitor of c-Myc inhibited PD-L1 expression and tumor growth. Using xenograft models, we demonstrated that the combination of JQ1 and anti-PD-L1 antibody exerted synergistic inhibition of PDAC growth. Our data demonstrated that the expression of PD-L1 and c-Myc may be helpful prognostic biomarkers, and their inhibition may potentially serve as an effective treatment for PDAC. |
| first_indexed | 2024-12-13T13:23:57Z |
| format | Article |
| id | doaj.art-4cf5a9b303124645add3582abaab0e4e |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-13T13:23:57Z |
| publishDate | 2019-05-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-4cf5a9b303124645add3582abaab0e4e2022-12-21T23:44:21ZengTaylor & Francis GroupOncoImmunology2162-402X2019-05-018510.1080/2162402X.2019.15815291581529Synergistic inhibition of pancreatic cancer with anti-PD-L1 and c-Myc inhibitor JQ1Yu Pan0Qinglin Fei1Ping Xiong2Jianyang Yang3Zheyang Zhang4Xianchao Lin5Minggui Pan6Fengchun Lu7Heguang Huang8Fujian Medical University Union HospitalFujian Medical University Union Hospital900 Hospital of the Joint Logistics TeamFujian Medical University Union HospitalHarbin Medical UniversityFujian Medical University Union HospitalKaiser PermanenteFujian Medical University Union HospitalFujian Medical University Union HospitalHuman pancreatic ductal adenocarcinoma (PDAC) exhibits marginal responses to anti-PD-1/PD-L1 immunotherapy and its mechanism remains poorly understood. We have investigated the effect of anti-PD-L1 and c-Myc inhibition in PDAC. Using 87 patients with PDAC from our hospital database we found a significant correlation between the expression of PD-L1 and c-Myc. Moreover, the expression of both PD-L1 and c-Myc was associated with poor overall survival. In addition, we confirmed this finding with the PDAC patients in the TCGA database. Using several PDAC cell lines we demonstrated a significant correlation between the expression of PD-L1 and c-Myc. We also found that expression of PD-L1 correlated with high-grade histology. JQ1, an inhibitor of c-Myc inhibited PD-L1 expression and tumor growth. Using xenograft models, we demonstrated that the combination of JQ1 and anti-PD-L1 antibody exerted synergistic inhibition of PDAC growth. Our data demonstrated that the expression of PD-L1 and c-Myc may be helpful prognostic biomarkers, and their inhibition may potentially serve as an effective treatment for PDAC.http://dx.doi.org/10.1080/2162402X.2019.1581529c-mycpd-l1jq1immunotherapypancreatic cancer |
| spellingShingle | Yu Pan Qinglin Fei Ping Xiong Jianyang Yang Zheyang Zhang Xianchao Lin Minggui Pan Fengchun Lu Heguang Huang Synergistic inhibition of pancreatic cancer with anti-PD-L1 and c-Myc inhibitor JQ1 OncoImmunology c-myc pd-l1 jq1 immunotherapy pancreatic cancer |
| title | Synergistic inhibition of pancreatic cancer with anti-PD-L1 and c-Myc inhibitor JQ1 |
| title_full | Synergistic inhibition of pancreatic cancer with anti-PD-L1 and c-Myc inhibitor JQ1 |
| title_fullStr | Synergistic inhibition of pancreatic cancer with anti-PD-L1 and c-Myc inhibitor JQ1 |
| title_full_unstemmed | Synergistic inhibition of pancreatic cancer with anti-PD-L1 and c-Myc inhibitor JQ1 |
| title_short | Synergistic inhibition of pancreatic cancer with anti-PD-L1 and c-Myc inhibitor JQ1 |
| title_sort | synergistic inhibition of pancreatic cancer with anti pd l1 and c myc inhibitor jq1 |
| topic | c-myc pd-l1 jq1 immunotherapy pancreatic cancer |
| url | http://dx.doi.org/10.1080/2162402X.2019.1581529 |
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