SIGLEC11 promotes M2 macrophage polarization through AKT–mTOR signaling and facilitates the progression of gastric cancer

作者：Jingxin Yin, Lu Yang, Yihao Liu, Qimeng Shi, Minmin Shi, Zhenggang Zhu, Dong Fu, Zhenqiang Wang, Chen Li · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2025 · DOI：10.1136/jitc-2024-010162 · 被引用次数：20 · 研究领域：Immune cells in cancer、Glycosylation and Glycoproteins Research、Immunotherapy and Immune Responses

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...