The acidic tumor microenvironment enhances PD-L1 expression via activation of STAT3 in MDA-MB-231 breast cancer cells
Abstract Tumor acidosis, a common phenomenon in solid cancers such as breast cancer, is caused by the abnormal metabolism of cancer cells. The low pH affects cells surrounding the cancer, and tumor acidosis has been shown to inhibit the activity of immune cells. Despite many previous studies, the im...
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-022-09956-9 |
| _version_ | 1818505116853993472 |
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| author | Yong-Jin Kwon Eun-Bi Seo Ae Jin Jeong Song-Hee Lee Kum Hee Noh Sangsik Lee Chung-Hyun Cho Chang-Han Lee Hyun Mu Shin Hang-Rae Kim Hyeong-Gon Moon Sang-Kyu Ye |
| author_facet | Yong-Jin Kwon Eun-Bi Seo Ae Jin Jeong Song-Hee Lee Kum Hee Noh Sangsik Lee Chung-Hyun Cho Chang-Han Lee Hyun Mu Shin Hang-Rae Kim Hyeong-Gon Moon Sang-Kyu Ye |
| author_sort | Yong-Jin Kwon |
| collection | DOAJ |
| description | Abstract Tumor acidosis, a common phenomenon in solid cancers such as breast cancer, is caused by the abnormal metabolism of cancer cells. The low pH affects cells surrounding the cancer, and tumor acidosis has been shown to inhibit the activity of immune cells. Despite many previous studies, the immune surveillance mechanisms are not fully understood. We found that the expression of PD-L1 was significantly increased under conditions of extracellular acidosis in MDA-MB-231 cells. We also confirmed that the increased expression of PD-L1 mediated by extracellular acidosis was decreased when the pH was raised to the normal range. Gene set enrichment analysis (GSEA) of public breast cancer patient databases showed that PD-L1 expression was also highly correlated with IL-6/JAK/STAT3 signaling. Surprisingly, the expression of both phospho-tyrosine STAT3 and PD-L1 was significantly increased under conditions of extracellular acidosis, and inhibition of STAT3 did not increase the expression of PD-L1 even under acidic conditions in MDA-MB-231 cells. Based on these results, we suggest that the expression of PD-L1 is increased by tumor acidosis via activation of STAT3 in MDA-MB-231 cells. |
| first_indexed | 2024-12-10T21:46:21Z |
| format | Article |
| id | doaj.art-3c76d7a6e1f3484c9326417ca63283f0 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-10T21:46:21Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-3c76d7a6e1f3484c9326417ca63283f02022-12-22T01:32:21ZengBMCBMC Cancer1471-24072022-08-0122111110.1186/s12885-022-09956-9The acidic tumor microenvironment enhances PD-L1 expression via activation of STAT3 in MDA-MB-231 breast cancer cellsYong-Jin Kwon0Eun-Bi Seo1Ae Jin Jeong2Song-Hee Lee3Kum Hee Noh4Sangsik Lee5Chung-Hyun Cho6Chang-Han Lee7Hyun Mu Shin8Hang-Rae Kim9Hyeong-Gon Moon10Sang-Kyu Ye11Department of Pharmacology and Biomedical Sciences, Seoul National University College of MedicineDepartment of Pharmacology and Biomedical Sciences, Seoul National University College of MedicineDepartment of Pharmacology and Biomedical Sciences, Seoul National University College of MedicineDepartment of Pharmacology and Biomedical Sciences, Seoul National University College of MedicineDepartment of Pharmacology and Biomedical Sciences, Seoul National University College of MedicineDepartment of Biomedical Engineering, Catholic Kwangdong University College of Medical ConvergenceDepartment of Pharmacology and Biomedical Sciences, Seoul National University College of MedicineDepartment of Pharmacology and Biomedical Sciences, Seoul National University College of MedicineWide River Institute of Immunology, Seoul National UniversityDepartment of Anatomy and Cell Biology, Seoul National University College of MedicineDepartment of Surgery, Seoul National University College of MedicineDepartment of Pharmacology and Biomedical Sciences, Seoul National University College of MedicineAbstract Tumor acidosis, a common phenomenon in solid cancers such as breast cancer, is caused by the abnormal metabolism of cancer cells. The low pH affects cells surrounding the cancer, and tumor acidosis has been shown to inhibit the activity of immune cells. Despite many previous studies, the immune surveillance mechanisms are not fully understood. We found that the expression of PD-L1 was significantly increased under conditions of extracellular acidosis in MDA-MB-231 cells. We also confirmed that the increased expression of PD-L1 mediated by extracellular acidosis was decreased when the pH was raised to the normal range. Gene set enrichment analysis (GSEA) of public breast cancer patient databases showed that PD-L1 expression was also highly correlated with IL-6/JAK/STAT3 signaling. Surprisingly, the expression of both phospho-tyrosine STAT3 and PD-L1 was significantly increased under conditions of extracellular acidosis, and inhibition of STAT3 did not increase the expression of PD-L1 even under acidic conditions in MDA-MB-231 cells. Based on these results, we suggest that the expression of PD-L1 is increased by tumor acidosis via activation of STAT3 in MDA-MB-231 cells.https://doi.org/10.1186/s12885-022-09956-9Extracellular acidosisImmune checkpointPD-L1STAT3MDA-MB-231 cells |
| spellingShingle | Yong-Jin Kwon Eun-Bi Seo Ae Jin Jeong Song-Hee Lee Kum Hee Noh Sangsik Lee Chung-Hyun Cho Chang-Han Lee Hyun Mu Shin Hang-Rae Kim Hyeong-Gon Moon Sang-Kyu Ye The acidic tumor microenvironment enhances PD-L1 expression via activation of STAT3 in MDA-MB-231 breast cancer cells BMC Cancer Extracellular acidosis Immune checkpoint PD-L1 STAT3 MDA-MB-231 cells |
| title | The acidic tumor microenvironment enhances PD-L1 expression via activation of STAT3 in MDA-MB-231 breast cancer cells |
| title_full | The acidic tumor microenvironment enhances PD-L1 expression via activation of STAT3 in MDA-MB-231 breast cancer cells |
| title_fullStr | The acidic tumor microenvironment enhances PD-L1 expression via activation of STAT3 in MDA-MB-231 breast cancer cells |
| title_full_unstemmed | The acidic tumor microenvironment enhances PD-L1 expression via activation of STAT3 in MDA-MB-231 breast cancer cells |
| title_short | The acidic tumor microenvironment enhances PD-L1 expression via activation of STAT3 in MDA-MB-231 breast cancer cells |
| title_sort | acidic tumor microenvironment enhances pd l1 expression via activation of stat3 in mda mb 231 breast cancer cells |
| topic | Extracellular acidosis Immune checkpoint PD-L1 STAT3 MDA-MB-231 cells |
| url | https://doi.org/10.1186/s12885-022-09956-9 |
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