PD-1/PD-L1, MDSC Pathways, and Checkpoint Inhibitor Therapy in <i>Ph</i>(-) Myeloproliferative Neoplasm: A Review
There has been significant progress in immune checkpoint inhibitor (CPI) therapy in many solid tumor types. However, only a single failed study has been published in treating <i>Ph(</i>-) myeloproliferative neoplasm (MPN). To make progress in CPI studies on this disease, herein, we revie...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/10/5837 |
| _version_ | 1797499087346466816 |
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| author | Jen-Chin Wang Lishi Sun |
| author_facet | Jen-Chin Wang Lishi Sun |
| author_sort | Jen-Chin Wang |
| collection | DOAJ |
| description | There has been significant progress in immune checkpoint inhibitor (CPI) therapy in many solid tumor types. However, only a single failed study has been published in treating <i>Ph(</i>-) myeloproliferative neoplasm (MPN). To make progress in CPI studies on this disease, herein, we review and summarize the mechanisms of activation of the PD-L1 promoter, which are as follows: (a) the extrinsic mechanism, which is activated by interferon gamma (IFN γ) by tumor infiltration lymphocytes (TIL) and NK cells; (b) the intrinsic mechanism of EGFR or PTEN loss resulting in the activation of the MAPK and AKT pathways and then stat 1 and 3 activation; and (c) 9p24 amplicon amplification, resulting in PD-L1 and Jak2 activation. We also review the literature and postulate that many of the failures of CPI therapy in MPN are likely due to excessive MDSC activities. We list all of the anti-MDSC agents, especially those with ruxolitinib, IMID compounds, and BTK inhibitors, which may be combined with CPI therapy in the future as part of clinical trials applying CPI therapy to <i>Ph</i>(-) MPN. |
| first_indexed | 2024-03-10T03:42:25Z |
| format | Article |
| id | doaj.art-5711953a824b4b418b8f654e4bc1875e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:42:25Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5711953a824b4b418b8f654e4bc1875e2023-11-23T11:29:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012310583710.3390/ijms23105837PD-1/PD-L1, MDSC Pathways, and Checkpoint Inhibitor Therapy in <i>Ph</i>(-) Myeloproliferative Neoplasm: A ReviewJen-Chin Wang0Lishi Sun1Division of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY 11212, USADivision of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY 11212, USAThere has been significant progress in immune checkpoint inhibitor (CPI) therapy in many solid tumor types. However, only a single failed study has been published in treating <i>Ph(</i>-) myeloproliferative neoplasm (MPN). To make progress in CPI studies on this disease, herein, we review and summarize the mechanisms of activation of the PD-L1 promoter, which are as follows: (a) the extrinsic mechanism, which is activated by interferon gamma (IFN γ) by tumor infiltration lymphocytes (TIL) and NK cells; (b) the intrinsic mechanism of EGFR or PTEN loss resulting in the activation of the MAPK and AKT pathways and then stat 1 and 3 activation; and (c) 9p24 amplicon amplification, resulting in PD-L1 and Jak2 activation. We also review the literature and postulate that many of the failures of CPI therapy in MPN are likely due to excessive MDSC activities. We list all of the anti-MDSC agents, especially those with ruxolitinib, IMID compounds, and BTK inhibitors, which may be combined with CPI therapy in the future as part of clinical trials applying CPI therapy to <i>Ph</i>(-) MPN.https://www.mdpi.com/1422-0067/23/10/5837myeloproliferative neoplasmmyeloid-derived suppressor cellsPD-1PD-L1myeloid suppressor cells (MDSC)immune checkpoint inhibitor therapy (CPI) |
| spellingShingle | Jen-Chin Wang Lishi Sun PD-1/PD-L1, MDSC Pathways, and Checkpoint Inhibitor Therapy in <i>Ph</i>(-) Myeloproliferative Neoplasm: A Review International Journal of Molecular Sciences myeloproliferative neoplasm myeloid-derived suppressor cells PD-1 PD-L1 myeloid suppressor cells (MDSC) immune checkpoint inhibitor therapy (CPI) |
| title | PD-1/PD-L1, MDSC Pathways, and Checkpoint Inhibitor Therapy in <i>Ph</i>(-) Myeloproliferative Neoplasm: A Review |
| title_full | PD-1/PD-L1, MDSC Pathways, and Checkpoint Inhibitor Therapy in <i>Ph</i>(-) Myeloproliferative Neoplasm: A Review |
| title_fullStr | PD-1/PD-L1, MDSC Pathways, and Checkpoint Inhibitor Therapy in <i>Ph</i>(-) Myeloproliferative Neoplasm: A Review |
| title_full_unstemmed | PD-1/PD-L1, MDSC Pathways, and Checkpoint Inhibitor Therapy in <i>Ph</i>(-) Myeloproliferative Neoplasm: A Review |
| title_short | PD-1/PD-L1, MDSC Pathways, and Checkpoint Inhibitor Therapy in <i>Ph</i>(-) Myeloproliferative Neoplasm: A Review |
| title_sort | pd 1 pd l1 mdsc pathways and checkpoint inhibitor therapy in i ph i myeloproliferative neoplasm a review |
| topic | myeloproliferative neoplasm myeloid-derived suppressor cells PD-1 PD-L1 myeloid suppressor cells (MDSC) immune checkpoint inhibitor therapy (CPI) |
| url | https://www.mdpi.com/1422-0067/23/10/5837 |
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