NLRP12/C1qA positive feedback in tumor-associated macrophages regulates immunosuppression through LILRB4/NF-κB pathway in lung adenocarcinoma
Abstract The anti-tumor immune response is greatly hindered by the protumor polarization of tumor-associated macrophages (TAMs). Cancer-related inflammation plays a central role in TAMs protumor polarization. Our study explored the unique positive feedback loop between inflammasome and complement in...
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| Format: | Article |
| Language: | English |
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Springer
2024-11-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-024-03880-6 |
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| _version_ | 1832571650163343360 |
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| author | Jiaxin Yin Yuxiao Song Yang Fu Jun Wang Zhimin Zhang Shasha Ruan Gaoli Liu Bicheng Zhang |
| author_facet | Jiaxin Yin Yuxiao Song Yang Fu Jun Wang Zhimin Zhang Shasha Ruan Gaoli Liu Bicheng Zhang |
| author_sort | Jiaxin Yin |
| collection | DOAJ |
| description | Abstract The anti-tumor immune response is greatly hindered by the protumor polarization of tumor-associated macrophages (TAMs). Cancer-related inflammation plays a central role in TAMs protumor polarization. Our study explored the unique positive feedback loop between inflammasome and complement in TAMs. The present study identified NOD-like receptors family pyrin domain containing 12 (NLRP12) formed positive feedback with C1qA and drove TAMs protumor polarization via the LILRB4/NF-κB pathway. In addition, NLRP12 was predominantly expressed in TAMs and was associated with poorer prognosis in lung adenocarcinoma (LUAD) patients. Knocking down LILRB4 inhibited TAMs protumor polarization. NLRP12-overexpressing TAMs promoted tumor cells’ malignant progression and inhibited T cells’ proliferation and cytotoxic function. Lastly, NLRP12 knockout (NLRP12−/−) reversed macrophage polarization, enhanced T-cell anti-tumor immunity, and suppressed tumor growth. Our findings highlighted the essential role of NLRP12/C1qA positive feedback loop and the LILRB4/NF-κB pathway in promoting TAMs protumor polarization. Inhibition of NLRP12 suppressed tumor development and promoted immune response. NLRP12 may be a promising target for LUAD immunotherapy. |
| format | Article |
| id | doaj-art-4960a066e5b04f439bbb76f6b8ffbc78 |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-4960a066e5b04f439bbb76f6b8ffbc782025-02-02T12:26:50ZengSpringerCancer Immunology, Immunotherapy1432-08512024-11-0174111810.1007/s00262-024-03880-6NLRP12/C1qA positive feedback in tumor-associated macrophages regulates immunosuppression through LILRB4/NF-κB pathway in lung adenocarcinomaJiaxin Yin0Yuxiao Song1Yang Fu2Jun Wang3Zhimin Zhang4Shasha Ruan5Gaoli Liu6Bicheng Zhang7Cancer Center, Renmin Hospital of Wuhan UniversityCancer Center, Renmin Hospital of Wuhan UniversityDepartment of Oncology, Xiangyang Hospital, Hubei University of Chinese MedicineDepartment of Oncology, The First Affiliated Hospital of Shandong First Medical UniversityCancer Center, Renmin Hospital of Wuhan UniversityCancer Center, Renmin Hospital of Wuhan UniversityDepartment of Thoracic Surgery, Renmin Hospital of Wuhan UniversityCancer Center, Renmin Hospital of Wuhan UniversityAbstract The anti-tumor immune response is greatly hindered by the protumor polarization of tumor-associated macrophages (TAMs). Cancer-related inflammation plays a central role in TAMs protumor polarization. Our study explored the unique positive feedback loop between inflammasome and complement in TAMs. The present study identified NOD-like receptors family pyrin domain containing 12 (NLRP12) formed positive feedback with C1qA and drove TAMs protumor polarization via the LILRB4/NF-κB pathway. In addition, NLRP12 was predominantly expressed in TAMs and was associated with poorer prognosis in lung adenocarcinoma (LUAD) patients. Knocking down LILRB4 inhibited TAMs protumor polarization. NLRP12-overexpressing TAMs promoted tumor cells’ malignant progression and inhibited T cells’ proliferation and cytotoxic function. Lastly, NLRP12 knockout (NLRP12−/−) reversed macrophage polarization, enhanced T-cell anti-tumor immunity, and suppressed tumor growth. Our findings highlighted the essential role of NLRP12/C1qA positive feedback loop and the LILRB4/NF-κB pathway in promoting TAMs protumor polarization. Inhibition of NLRP12 suppressed tumor development and promoted immune response. NLRP12 may be a promising target for LUAD immunotherapy.https://doi.org/10.1007/s00262-024-03880-6NLRP12Tumor-associated macrophagesC1qALILRB4NF-κBLung adenocarcinoma |
| spellingShingle | Jiaxin Yin Yuxiao Song Yang Fu Jun Wang Zhimin Zhang Shasha Ruan Gaoli Liu Bicheng Zhang NLRP12/C1qA positive feedback in tumor-associated macrophages regulates immunosuppression through LILRB4/NF-κB pathway in lung adenocarcinoma Cancer Immunology, Immunotherapy NLRP12 Tumor-associated macrophages C1qA LILRB4 NF-κB Lung adenocarcinoma |
| title | NLRP12/C1qA positive feedback in tumor-associated macrophages regulates immunosuppression through LILRB4/NF-κB pathway in lung adenocarcinoma |
| title_full | NLRP12/C1qA positive feedback in tumor-associated macrophages regulates immunosuppression through LILRB4/NF-κB pathway in lung adenocarcinoma |
| title_fullStr | NLRP12/C1qA positive feedback in tumor-associated macrophages regulates immunosuppression through LILRB4/NF-κB pathway in lung adenocarcinoma |
| title_full_unstemmed | NLRP12/C1qA positive feedback in tumor-associated macrophages regulates immunosuppression through LILRB4/NF-κB pathway in lung adenocarcinoma |
| title_short | NLRP12/C1qA positive feedback in tumor-associated macrophages regulates immunosuppression through LILRB4/NF-κB pathway in lung adenocarcinoma |
| title_sort | nlrp12 c1qa positive feedback in tumor associated macrophages regulates immunosuppression through lilrb4 nf κb pathway in lung adenocarcinoma |
| topic | NLRP12 Tumor-associated macrophages C1qA LILRB4 NF-κB Lung adenocarcinoma |
| url | https://doi.org/10.1007/s00262-024-03880-6 |
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