AIM2 fosters lung adenocarcinoma immune escape by modulating PD-L1 expression in tumor-associated macrophages via JAK/STAT3
This work was devised to discuss the effect of AIM2 on the immunosuppression of LUAD tumors, as well as its molecular mechanism. An allograft mouse model was built. Mouse macrophages were isolated and collected. The infiltration level of Mø and expression of M1 Mø, M2 Mø markers, and PD-L1 were assa...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21645515.2023.2269790 |
| _version_ | 1797633752352948224 |
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| author | Hua Ye Wenwen Yu Yunlei Li Xiaoqiong Bao Yangyang Ni Xiangxiang Chen Yangjie Sun Ali Chen Weilong Zhou Jifa Li |
| author_facet | Hua Ye Wenwen Yu Yunlei Li Xiaoqiong Bao Yangyang Ni Xiangxiang Chen Yangjie Sun Ali Chen Weilong Zhou Jifa Li |
| author_sort | Hua Ye |
| collection | DOAJ |
| description | This work was devised to discuss the effect of AIM2 on the immunosuppression of LUAD tumors, as well as its molecular mechanism. An allograft mouse model was built. Mouse macrophages were isolated and collected. The infiltration level of Mø and expression of M1 Mø, M2 Mø markers, and PD-L1 were assayed by IHC and flow cytometry. Expression levels of M1 Mø and M2 Mø marker genes and PD-L1 were detected by qPCR. The expression of proteins linked with JAK/STAT3 was tested by western blot. CD8+T cells and NK cells were activated in vitro and co-cultured with mouse macrophages, and their cytotoxicity was detected by LDH method. The proportion of CD206+PD-L1+ cells and the activation and proliferation of CD8+T cells were assayed by flow cytometry. Multicolor immunofluorescence was utilized to assay the co-localization of proteins. AIM2 demonstrated a high expression in LUAD, exhibiting a conspicuous positive correlation with the expression of the M2 Mø markers as well as PD-L1. Expression of M1 markers was upregulated after knockdown of AIM2, while M2 markers expression and PD-L1 were downregulated, and the colocalization of proteins linked with PD-L1 and M2 Mø was decreased. The infiltration and cytotoxicity of CD8+T cells and NK cells increased after silencing AIM2. After the knockdown of AIM2, which was enriched in the JAK/STAT3 pathway, the phosphorylation levels of JAK1, JAK2, and STAT3 were reduced, the immune infiltration level of CD8+T cells increased, and the co-localization level of PD-L1 and PD-1 dropped. The activity and proliferation level of CD8+T cells were increased with the reduced PD-1 expression. AIM2 fosters M2 Mø polarization and PD-L1 expression via the JAK/STAT3 pathway. Moreover, AIM2 promotes the immune escape of LUAD via the PD-1/PD-L1 axis. Our work may blaze a trail for the clinical treatment of LUAD. |
| first_indexed | 2024-03-11T11:58:16Z |
| format | Article |
| id | doaj.art-e96d104679054550b9ba23deca2196dc |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T11:58:16Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-e96d104679054550b9ba23deca2196dc2023-11-08T11:55:20ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2023-12-0119310.1080/21645515.2023.22697902269790AIM2 fosters lung adenocarcinoma immune escape by modulating PD-L1 expression in tumor-associated macrophages via JAK/STAT3Hua Ye0Wenwen Yu1Yunlei Li2Xiaoqiong Bao3Yangyang Ni4Xiangxiang Chen5Yangjie Sun6Ali Chen7Weilong Zhou8Jifa Li9Wenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityThis work was devised to discuss the effect of AIM2 on the immunosuppression of LUAD tumors, as well as its molecular mechanism. An allograft mouse model was built. Mouse macrophages were isolated and collected. The infiltration level of Mø and expression of M1 Mø, M2 Mø markers, and PD-L1 were assayed by IHC and flow cytometry. Expression levels of M1 Mø and M2 Mø marker genes and PD-L1 were detected by qPCR. The expression of proteins linked with JAK/STAT3 was tested by western blot. CD8+T cells and NK cells were activated in vitro and co-cultured with mouse macrophages, and their cytotoxicity was detected by LDH method. The proportion of CD206+PD-L1+ cells and the activation and proliferation of CD8+T cells were assayed by flow cytometry. Multicolor immunofluorescence was utilized to assay the co-localization of proteins. AIM2 demonstrated a high expression in LUAD, exhibiting a conspicuous positive correlation with the expression of the M2 Mø markers as well as PD-L1. Expression of M1 markers was upregulated after knockdown of AIM2, while M2 markers expression and PD-L1 were downregulated, and the colocalization of proteins linked with PD-L1 and M2 Mø was decreased. The infiltration and cytotoxicity of CD8+T cells and NK cells increased after silencing AIM2. After the knockdown of AIM2, which was enriched in the JAK/STAT3 pathway, the phosphorylation levels of JAK1, JAK2, and STAT3 were reduced, the immune infiltration level of CD8+T cells increased, and the co-localization level of PD-L1 and PD-1 dropped. The activity and proliferation level of CD8+T cells were increased with the reduced PD-1 expression. AIM2 fosters M2 Mø polarization and PD-L1 expression via the JAK/STAT3 pathway. Moreover, AIM2 promotes the immune escape of LUAD via the PD-1/PD-L1 axis. Our work may blaze a trail for the clinical treatment of LUAD.http://dx.doi.org/10.1080/21645515.2023.2269790aim2jak/stat3tumor-associated macrophagepd-l1lung adenocarcinomaimmune escape |
| spellingShingle | Hua Ye Wenwen Yu Yunlei Li Xiaoqiong Bao Yangyang Ni Xiangxiang Chen Yangjie Sun Ali Chen Weilong Zhou Jifa Li AIM2 fosters lung adenocarcinoma immune escape by modulating PD-L1 expression in tumor-associated macrophages via JAK/STAT3 Human Vaccines & Immunotherapeutics aim2 jak/stat3 tumor-associated macrophage pd-l1 lung adenocarcinoma immune escape |
| title | AIM2 fosters lung adenocarcinoma immune escape by modulating PD-L1 expression in tumor-associated macrophages via JAK/STAT3 |
| title_full | AIM2 fosters lung adenocarcinoma immune escape by modulating PD-L1 expression in tumor-associated macrophages via JAK/STAT3 |
| title_fullStr | AIM2 fosters lung adenocarcinoma immune escape by modulating PD-L1 expression in tumor-associated macrophages via JAK/STAT3 |
| title_full_unstemmed | AIM2 fosters lung adenocarcinoma immune escape by modulating PD-L1 expression in tumor-associated macrophages via JAK/STAT3 |
| title_short | AIM2 fosters lung adenocarcinoma immune escape by modulating PD-L1 expression in tumor-associated macrophages via JAK/STAT3 |
| title_sort | aim2 fosters lung adenocarcinoma immune escape by modulating pd l1 expression in tumor associated macrophages via jak stat3 |
| topic | aim2 jak/stat3 tumor-associated macrophage pd-l1 lung adenocarcinoma immune escape |
| url | http://dx.doi.org/10.1080/21645515.2023.2269790 |
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