SIGLEC11 promotes M2 macrophage polarization through AKT–mTOR signaling and facilitates the progression of gastric cancer
Background Sialic acid-binding immunoglobulin-like lectins (SIGLECs) are widely expressed on immune cell surfaces, play an important role in maintaining immune homeostasis and regulating inflammatory responses, and are increasingly emerging as potential targets for tumor immunotherapy. However, the...
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BMJ Publishing Group
2025-01-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/1/e010162.full |
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| author | Chen Li Yang Lu Yihao Liu Minmin Shi Zhenggang Zhu Jingxin Yin Qimeng Shi Da Fu Zhenqiang Wang |
| author_facet | Chen Li Yang Lu Yihao Liu Minmin Shi Zhenggang Zhu Jingxin Yin Qimeng Shi Da Fu Zhenqiang Wang |
| author_sort | Chen Li |
| collection | DOAJ |
| description | Background Sialic acid-binding immunoglobulin-like lectins (SIGLECs) are widely expressed on immune cell surfaces, play an important role in maintaining immune homeostasis and regulating inflammatory responses, and are increasingly emerging as potential targets for tumor immunotherapy. However, the expression profile and crucial role of SIGLEC11 in gastric cancer (GC) remain unclear. This study aimed to elucidate the prognostic relevance of SIGLEC11 expression and its role in the immune microenvironment in patients with GC.Methods SIGLEC11 expression profile was analyzed using bioinformatics, immunohistochemistry, and immunofluorescence staining. Flow cytometry, mouse tumor models, patient-derived tumor organoid models, and RNA sequencing were used to explore the potential functions with the underlying mechanisms of SIGLEC11 in a coculture system of macrophages and GC cells.Results We demonstrated that SIGLEC11 was predominantly expressed in normal tissues. However, tumor-infiltrating SIGLEC11+ cells in the high SIGLEC11 expression subgroups showed poor overall survival, which was associated with the expression of an immunosuppressive regulator. Our results showed that SIGLEC11 was predominantly expressed in monocytes and macrophages and selectively upregulated in tumor-associated macrophages. Furthermore, SIGLEC11 promoted macrophage M2 polarization via AKT–mTOR signaling. In addition, SIGLEC11+ macrophages accelerate GC progression.Conclusions The abundance of SIGLEC11+ M2-like macrophage-infiltrating tumors may serve as a biomarker for identifying immunosuppressive subtypes of GC. Thus, the potential role of SIGLEC11+ M2 macrophages as therapeutic targets warrants further investigation. |
| format | Article |
| id | doaj-art-0096964c9d6042dda72c2538449b5864 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-0096964c9d6042dda72c2538449b58642025-01-05T05:35:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-01-0113110.1136/jitc-2024-010162SIGLEC11 promotes M2 macrophage polarization through AKT–mTOR signaling and facilitates the progression of gastric cancerChen Li0Yang Lu1Yihao Liu2Minmin Shi3Zhenggang Zhu4Jingxin Yin5Qimeng Shi6Da Fu7Zhenqiang Wang81 Department of Vascular Neurosurgery, New Era Stroke Care and Research Institute, the PLA Rocket Force General Hospital, Beijing, China1 Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaResearch Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China1 Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People`s Republic of ChinaShanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBackground Sialic acid-binding immunoglobulin-like lectins (SIGLECs) are widely expressed on immune cell surfaces, play an important role in maintaining immune homeostasis and regulating inflammatory responses, and are increasingly emerging as potential targets for tumor immunotherapy. However, the expression profile and crucial role of SIGLEC11 in gastric cancer (GC) remain unclear. This study aimed to elucidate the prognostic relevance of SIGLEC11 expression and its role in the immune microenvironment in patients with GC.Methods SIGLEC11 expression profile was analyzed using bioinformatics, immunohistochemistry, and immunofluorescence staining. Flow cytometry, mouse tumor models, patient-derived tumor organoid models, and RNA sequencing were used to explore the potential functions with the underlying mechanisms of SIGLEC11 in a coculture system of macrophages and GC cells.Results We demonstrated that SIGLEC11 was predominantly expressed in normal tissues. However, tumor-infiltrating SIGLEC11+ cells in the high SIGLEC11 expression subgroups showed poor overall survival, which was associated with the expression of an immunosuppressive regulator. Our results showed that SIGLEC11 was predominantly expressed in monocytes and macrophages and selectively upregulated in tumor-associated macrophages. Furthermore, SIGLEC11 promoted macrophage M2 polarization via AKT–mTOR signaling. In addition, SIGLEC11+ macrophages accelerate GC progression.Conclusions The abundance of SIGLEC11+ M2-like macrophage-infiltrating tumors may serve as a biomarker for identifying immunosuppressive subtypes of GC. Thus, the potential role of SIGLEC11+ M2 macrophages as therapeutic targets warrants further investigation.https://jitc.bmj.com/content/13/1/e010162.full |
| spellingShingle | Chen Li Yang Lu Yihao Liu Minmin Shi Zhenggang Zhu Jingxin Yin Qimeng Shi Da Fu Zhenqiang Wang SIGLEC11 promotes M2 macrophage polarization through AKT–mTOR signaling and facilitates the progression of gastric cancer Journal for ImmunoTherapy of Cancer |
| title | SIGLEC11 promotes M2 macrophage polarization through AKT–mTOR signaling and facilitates the progression of gastric cancer |
| title_full | SIGLEC11 promotes M2 macrophage polarization through AKT–mTOR signaling and facilitates the progression of gastric cancer |
| title_fullStr | SIGLEC11 promotes M2 macrophage polarization through AKT–mTOR signaling and facilitates the progression of gastric cancer |
| title_full_unstemmed | SIGLEC11 promotes M2 macrophage polarization through AKT–mTOR signaling and facilitates the progression of gastric cancer |
| title_short | SIGLEC11 promotes M2 macrophage polarization through AKT–mTOR signaling and facilitates the progression of gastric cancer |
| title_sort | siglec11 promotes m2 macrophage polarization through akt mtor signaling and facilitates the progression of gastric cancer |
| url | https://jitc.bmj.com/content/13/1/e010162.full |
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