MDSC suppresses T cell antitumor immunity in CAC via GPNMB in a MyD88‐dependent manner
Abstract Background Myeloid‐derived suppressor cells (MDSCs) played an essential role in tumor microenvironment to suppress host antitumor immunity and help cancer cells escape immune surveillance. However, the molecular mechanism behind tumor evasion mediated by MDSCs is not fully understood. Glyco...
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.6887 |
| _version_ | 1797277166193344512 |
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| author | Bo Wang Lu Wang Runshi Shang Lin Xie |
| author_facet | Bo Wang Lu Wang Runshi Shang Lin Xie |
| author_sort | Bo Wang |
| collection | DOAJ |
| description | Abstract Background Myeloid‐derived suppressor cells (MDSCs) played an essential role in tumor microenvironment to suppress host antitumor immunity and help cancer cells escape immune surveillance. However, the molecular mechanism behind tumor evasion mediated by MDSCs is not fully understood. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is considered to associate with tumor initiation, metastasis and angiogenesis. Blocking GPNMB function is a potentially valuable therapy for cancer by eliminating GPNMB+MDSCs. Our previous study has proved that blockage the MyD88 signaling with the MyD88 inhibitor, TJ‐M2010‐5, may completely prevent the development of CAC in mice, accompanying with downregulation of GPNMB mRNA in the inhibitor‐treated mice of CAC. Methods We here focus on the underlying the relationship between GPNMB function and MyD88 signaling pathway activation in MDSCs' antitumor activity in CAC. Results CAC development in the mouse model is associated with expanded GPNMB+MDSCs by a MyD88‐dependent pathway. The GPNMB expression on MDSCs is associated with MyD88 signaling activation. The inhibitory effect of MDSCs on T cell proliferation, activation and antitumor cytotoxicity in CAC is mediated by GPNMB in a MyD8‐dependent manner. Conclusion MyD88 signaling pathway plays an essential role in GPNMB+MDSC‐mediated tumor immune escape during CAC development and is a promising focus for revealing the mechanisms of MDSC that facilitate immunosuppression and tumor progression. |
| first_indexed | 2024-03-07T15:43:47Z |
| format | Article |
| id | doaj.art-9f742887e51b43e2bb270673edf69ad0 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-07T15:43:47Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-9f742887e51b43e2bb270673edf69ad02024-03-05T06:22:52ZengWileyCancer Medicine2045-76342024-01-01131n/an/a10.1002/cam4.6887MDSC suppresses T cell antitumor immunity in CAC via GPNMB in a MyD88‐dependent mannerBo Wang0Lu Wang1Runshi Shang2Lin Xie3Department of Gastroenterology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaInstitute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences Wuhan ChinaInstitute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences Wuhan ChinaInstitute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences Wuhan ChinaAbstract Background Myeloid‐derived suppressor cells (MDSCs) played an essential role in tumor microenvironment to suppress host antitumor immunity and help cancer cells escape immune surveillance. However, the molecular mechanism behind tumor evasion mediated by MDSCs is not fully understood. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is considered to associate with tumor initiation, metastasis and angiogenesis. Blocking GPNMB function is a potentially valuable therapy for cancer by eliminating GPNMB+MDSCs. Our previous study has proved that blockage the MyD88 signaling with the MyD88 inhibitor, TJ‐M2010‐5, may completely prevent the development of CAC in mice, accompanying with downregulation of GPNMB mRNA in the inhibitor‐treated mice of CAC. Methods We here focus on the underlying the relationship between GPNMB function and MyD88 signaling pathway activation in MDSCs' antitumor activity in CAC. Results CAC development in the mouse model is associated with expanded GPNMB+MDSCs by a MyD88‐dependent pathway. The GPNMB expression on MDSCs is associated with MyD88 signaling activation. The inhibitory effect of MDSCs on T cell proliferation, activation and antitumor cytotoxicity in CAC is mediated by GPNMB in a MyD8‐dependent manner. Conclusion MyD88 signaling pathway plays an essential role in GPNMB+MDSC‐mediated tumor immune escape during CAC development and is a promising focus for revealing the mechanisms of MDSC that facilitate immunosuppression and tumor progression.https://doi.org/10.1002/cam4.6887colitis‐associated colorectal cancerGPNMBMDSCMyD88 signalingT cell immunity |
| spellingShingle | Bo Wang Lu Wang Runshi Shang Lin Xie MDSC suppresses T cell antitumor immunity in CAC via GPNMB in a MyD88‐dependent manner Cancer Medicine colitis‐associated colorectal cancer GPNMB MDSC MyD88 signaling T cell immunity |
| title | MDSC suppresses T cell antitumor immunity in CAC via GPNMB in a MyD88‐dependent manner |
| title_full | MDSC suppresses T cell antitumor immunity in CAC via GPNMB in a MyD88‐dependent manner |
| title_fullStr | MDSC suppresses T cell antitumor immunity in CAC via GPNMB in a MyD88‐dependent manner |
| title_full_unstemmed | MDSC suppresses T cell antitumor immunity in CAC via GPNMB in a MyD88‐dependent manner |
| title_short | MDSC suppresses T cell antitumor immunity in CAC via GPNMB in a MyD88‐dependent manner |
| title_sort | mdsc suppresses t cell antitumor immunity in cac via gpnmb in a myd88 dependent manner |
| topic | colitis‐associated colorectal cancer GPNMB MDSC MyD88 signaling T cell immunity |
| url | https://doi.org/10.1002/cam4.6887 |
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