Methionine restriction promotes the polarization of macrophages towards M1 and the immunotherapy effect of PD-L1/PD-1 blockades by inhibiting the secretion of MIF by gastric carcinoma cells
Background: The limited curative effect of PD-L1/PD-1 blockades presents challenges to immunotherapy for advanced gastric cancer. We have found that methionine restriction (MR) enhances the drug resistance of gastric carcinoma cells. We aimed to explore whether MR can enhance the efficacy of PD-L1/P...
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Elsevier
2025-01-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523324003073 |
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| author | Lin Xin Jiang Liu Jun-Yan Lai He-Song Xu Luo-Jun Fan Yong-Hui Zou Qi Zhou Zhen- Qi Yue Jin-Heng Gan |
| author_facet | Lin Xin Jiang Liu Jun-Yan Lai He-Song Xu Luo-Jun Fan Yong-Hui Zou Qi Zhou Zhen- Qi Yue Jin-Heng Gan |
| author_sort | Lin Xin |
| collection | DOAJ |
| description | Background: The limited curative effect of PD-L1/PD-1 blockades presents challenges to immunotherapy for advanced gastric cancer. We have found that methionine restriction (MR) enhances the drug resistance of gastric carcinoma cells. We aimed to explore whether MR can enhance the efficacy of PD-L1/PD-1 blockades in gastric cancer. Methods: To conduct MR, gastric carcinoma cells were transfected with LV-METase in vitro, and 615 mice were injected with MFC cells with stable METase expression in vivo. Flow cytometry was conducted to measure the proportions of M1/M2 macrophages and CD8+ GZMB+/IFN-γ+ T cells. Additionally, the levels of M1/M2 macrophage markers and MIF were also detected. Results: MR increased M1 and down-regulated M2 macrophages. MR suppressed MIF levels in gastric carcinoma cells, while the addition of anti-MIF neutralizing antibody inhibited the effect of MR on macrophage M1/M2 polarization. MR enhanced the increase of the proportion of CD8+ GZMB+ T cells and CD8+ IFN-γ+ T cells induced by PD-L1/PD-1 blockades. In vivo detection verified the efficacy of the combination of MR and PD-L1/PD-1 blockades on gastric cancer. Conclusions: MR inhibits the secretion of MIF by gastric carcinoma cells, promotes macrophage M1 polarization, and enhances the therapeutic effect of PD-L1/PD-1 blockades in gastric cancer. |
| format | Article |
| id | doaj-art-e2bd8ec6a52d461d8ae0db25ca2651d2 |
| institution | OA Journals |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-e2bd8ec6a52d461d8ae0db25ca2651d22025-08-20T02:30:39ZengElsevierTranslational Oncology1936-52332025-01-015110218110.1016/j.tranon.2024.102181Methionine restriction promotes the polarization of macrophages towards M1 and the immunotherapy effect of PD-L1/PD-1 blockades by inhibiting the secretion of MIF by gastric carcinoma cellsLin Xin0Jiang Liu1Jun-Yan Lai2He-Song Xu3Luo-Jun Fan4Yong-Hui Zou5Qi Zhou6Zhen- Qi Yue7Jin-Heng Gan8Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China; Intelligent Medical Imaging of Jiangxi Key Laboratory, Nanchang 330006, China; Corresponding author at: Mailing address: Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Address: No. 1 Minde Road, Donghu District, Nanchang 330006, Jiangxi, China.Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, ChinaClass 2210, The Second clinical medical college, Nanchang University, Nanchang, 330006, Jiangxi Province, ChinaDepartment of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, ChinaDepartment of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, ChinaDepartment of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, ChinaDepartment of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, ChinaDepartment of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, ChinaDepartment of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, ChinaBackground: The limited curative effect of PD-L1/PD-1 blockades presents challenges to immunotherapy for advanced gastric cancer. We have found that methionine restriction (MR) enhances the drug resistance of gastric carcinoma cells. We aimed to explore whether MR can enhance the efficacy of PD-L1/PD-1 blockades in gastric cancer. Methods: To conduct MR, gastric carcinoma cells were transfected with LV-METase in vitro, and 615 mice were injected with MFC cells with stable METase expression in vivo. Flow cytometry was conducted to measure the proportions of M1/M2 macrophages and CD8+ GZMB+/IFN-γ+ T cells. Additionally, the levels of M1/M2 macrophage markers and MIF were also detected. Results: MR increased M1 and down-regulated M2 macrophages. MR suppressed MIF levels in gastric carcinoma cells, while the addition of anti-MIF neutralizing antibody inhibited the effect of MR on macrophage M1/M2 polarization. MR enhanced the increase of the proportion of CD8+ GZMB+ T cells and CD8+ IFN-γ+ T cells induced by PD-L1/PD-1 blockades. In vivo detection verified the efficacy of the combination of MR and PD-L1/PD-1 blockades on gastric cancer. Conclusions: MR inhibits the secretion of MIF by gastric carcinoma cells, promotes macrophage M1 polarization, and enhances the therapeutic effect of PD-L1/PD-1 blockades in gastric cancer.http://www.sciencedirect.com/science/article/pii/S1936523324003073Methionine restrictionMIFGastric cancerPD-L1/PD-1 blockerMacrophage polarization |
| spellingShingle | Lin Xin Jiang Liu Jun-Yan Lai He-Song Xu Luo-Jun Fan Yong-Hui Zou Qi Zhou Zhen- Qi Yue Jin-Heng Gan Methionine restriction promotes the polarization of macrophages towards M1 and the immunotherapy effect of PD-L1/PD-1 blockades by inhibiting the secretion of MIF by gastric carcinoma cells Translational Oncology Methionine restriction MIF Gastric cancer PD-L1/PD-1 blocker Macrophage polarization |
| title | Methionine restriction promotes the polarization of macrophages towards M1 and the immunotherapy effect of PD-L1/PD-1 blockades by inhibiting the secretion of MIF by gastric carcinoma cells |
| title_full | Methionine restriction promotes the polarization of macrophages towards M1 and the immunotherapy effect of PD-L1/PD-1 blockades by inhibiting the secretion of MIF by gastric carcinoma cells |
| title_fullStr | Methionine restriction promotes the polarization of macrophages towards M1 and the immunotherapy effect of PD-L1/PD-1 blockades by inhibiting the secretion of MIF by gastric carcinoma cells |
| title_full_unstemmed | Methionine restriction promotes the polarization of macrophages towards M1 and the immunotherapy effect of PD-L1/PD-1 blockades by inhibiting the secretion of MIF by gastric carcinoma cells |
| title_short | Methionine restriction promotes the polarization of macrophages towards M1 and the immunotherapy effect of PD-L1/PD-1 blockades by inhibiting the secretion of MIF by gastric carcinoma cells |
| title_sort | methionine restriction promotes the polarization of macrophages towards m1 and the immunotherapy effect of pd l1 pd 1 blockades by inhibiting the secretion of mif by gastric carcinoma cells |
| topic | Methionine restriction MIF Gastric cancer PD-L1/PD-1 blocker Macrophage polarization |
| url | http://www.sciencedirect.com/science/article/pii/S1936523324003073 |
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