Tumor Cell-Intrinsic BTLA Receptor Inhibits the Proliferation of Tumor Cells via ERK1/2
B and T lymphocyte attenuator (BTLA) is an immune checkpoint molecule that mediates the escape of tumor cells from immunosurveillance. Consequently, BTLA and its ligand herpesvirus entry mediator (HVEM) are potentially immunotherapeutic targets. However, the potential effects of BTLA on tumor cells...
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| Format: | Article |
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MDPI AG
2022-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/24/4021 |
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| author | Tian-You Cheng Ya-Juan Liu Hong Yan Yi-Bo Xi Li-Qiang Duan Yang Wang Tian-Tian Zhang Yin-Min Gu Xiao-Dong Wang Chang-Xin Wu Shan Gao |
| author_facet | Tian-You Cheng Ya-Juan Liu Hong Yan Yi-Bo Xi Li-Qiang Duan Yang Wang Tian-Tian Zhang Yin-Min Gu Xiao-Dong Wang Chang-Xin Wu Shan Gao |
| author_sort | Tian-You Cheng |
| collection | DOAJ |
| description | B and T lymphocyte attenuator (BTLA) is an immune checkpoint molecule that mediates the escape of tumor cells from immunosurveillance. Consequently, BTLA and its ligand herpesvirus entry mediator (HVEM) are potentially immunotherapeutic targets. However, the potential effects of BTLA on tumor cells remain incompletely unknown. Here, we show that BTLA is expressed across a broad range of tumor cells. The depletion of BTLA or HVEM promotes cell proliferation and colony formation, which is reversed by the overexpression of BTLA in BTLA knockout cells. In contrast, overexpression of BTLA or HVEM inhibits tumor cell proliferation and colony formation. Furthermore, the proliferation of a subpopulation with high BTLA was also significantly slower than that of the low BTLA subpopulation. Mechanistically, the coordination of BTLA and HVEM inhibits its major downstream extracellular regulated protein kinase (ERK1/2) signaling pathway, thus preventing tumor cell growth. This study demonstrates that tumor cell-intrinsic BTLA/HVEM is a potential tumor suppressor and is likely to have a potential antagonist for immunotherapy, thus representing a potential biomarker for the optimal cancer immunotherapeutic treatment. |
| first_indexed | 2024-03-09T17:12:57Z |
| format | Article |
| id | doaj.art-0456426b906b4e199c54fce582c50cf5 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:12:57Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-0456426b906b4e199c54fce582c50cf52023-11-24T13:54:28ZengMDPI AGCells2073-44092022-12-011124402110.3390/cells11244021Tumor Cell-Intrinsic BTLA Receptor Inhibits the Proliferation of Tumor Cells via ERK1/2Tian-You Cheng0Ya-Juan Liu1Hong Yan2Yi-Bo Xi3Li-Qiang Duan4Yang Wang5Tian-Tian Zhang6Yin-Min Gu7Xiao-Dong Wang8Chang-Xin Wu9Shan Gao10Shanxi Academy of Advanced Research and Innovation, Taiyuan 030032, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan 030032, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan 030032, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan 030032, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan 030032, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan 030032, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan 030032, ChinaZhongda Hospital, Medical School, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, ChinaSuzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan 030032, ChinaShanxi Academy of Advanced Research and Innovation, Taiyuan 030032, ChinaB and T lymphocyte attenuator (BTLA) is an immune checkpoint molecule that mediates the escape of tumor cells from immunosurveillance. Consequently, BTLA and its ligand herpesvirus entry mediator (HVEM) are potentially immunotherapeutic targets. However, the potential effects of BTLA on tumor cells remain incompletely unknown. Here, we show that BTLA is expressed across a broad range of tumor cells. The depletion of BTLA or HVEM promotes cell proliferation and colony formation, which is reversed by the overexpression of BTLA in BTLA knockout cells. In contrast, overexpression of BTLA or HVEM inhibits tumor cell proliferation and colony formation. Furthermore, the proliferation of a subpopulation with high BTLA was also significantly slower than that of the low BTLA subpopulation. Mechanistically, the coordination of BTLA and HVEM inhibits its major downstream extracellular regulated protein kinase (ERK1/2) signaling pathway, thus preventing tumor cell growth. This study demonstrates that tumor cell-intrinsic BTLA/HVEM is a potential tumor suppressor and is likely to have a potential antagonist for immunotherapy, thus representing a potential biomarker for the optimal cancer immunotherapeutic treatment.https://www.mdpi.com/2073-4409/11/24/4021immune checkpointtumor cell-intrinsic BTLAtumor cell-intrinsic HVEMtumor suppressortherapeutic target |
| spellingShingle | Tian-You Cheng Ya-Juan Liu Hong Yan Yi-Bo Xi Li-Qiang Duan Yang Wang Tian-Tian Zhang Yin-Min Gu Xiao-Dong Wang Chang-Xin Wu Shan Gao Tumor Cell-Intrinsic BTLA Receptor Inhibits the Proliferation of Tumor Cells via ERK1/2 Cells immune checkpoint tumor cell-intrinsic BTLA tumor cell-intrinsic HVEM tumor suppressor therapeutic target |
| title | Tumor Cell-Intrinsic BTLA Receptor Inhibits the Proliferation of Tumor Cells via ERK1/2 |
| title_full | Tumor Cell-Intrinsic BTLA Receptor Inhibits the Proliferation of Tumor Cells via ERK1/2 |
| title_fullStr | Tumor Cell-Intrinsic BTLA Receptor Inhibits the Proliferation of Tumor Cells via ERK1/2 |
| title_full_unstemmed | Tumor Cell-Intrinsic BTLA Receptor Inhibits the Proliferation of Tumor Cells via ERK1/2 |
| title_short | Tumor Cell-Intrinsic BTLA Receptor Inhibits the Proliferation of Tumor Cells via ERK1/2 |
| title_sort | tumor cell intrinsic btla receptor inhibits the proliferation of tumor cells via erk1 2 |
| topic | immune checkpoint tumor cell-intrinsic BTLA tumor cell-intrinsic HVEM tumor suppressor therapeutic target |
| url | https://www.mdpi.com/2073-4409/11/24/4021 |
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