Suppression of AGRN enhances CD8+ T cell recruitment and inhibits breast cancer progression

Abstract Breast cancer (BC) stands as a prominent contributor to global cancer‐related mortality, with an increasing incidence annually. This study aims to investigate AGRN gene expression in BC, as well as explore its influence on the tumor immune microenvironment. AGRN displayed a pronounced upregulation in BC tissues relative to paracancerous tissues. Single‐cell RNA analysis highlighted AGRN‐specific elevation within cancer cell clusters and also showed expression expressed in stromal as well as immune cell clusters. AGRN upregulation was positively correlated with clinicopathological stage and negatively correlated with BC prognosis. As revealed by the in vitro experiment, AGRN knockdown effectively hinders BC cells in terms of proliferation, invasion as well as migration. AGRN protein, which may interact with EXT1, LRP4, RAPSN, etc., was primarily distributed in the cell cytoplasm. Notably, immune factors might interact with AGRN in BC, evidenced by its discernible associations with immunofactors like IL10, CD274, and PVRL2. Mass spectrometry and immunohistochemistry revealed that the reduction of AGRN led to an increase in CD8 + T cells with triple‐negative breast cancer (TNBC). Mechanistically, the connection between TRIM7 and PD‐L1 is improved by AGRN, acting as a scaffold, thereby facilitating the accelerated degradation of PD‐L1 by TRIM7. Downregulation of AGRN inhibits BC progression and increases CD8 + T cell recruitment. Targeting AGRN may contribute to BC treatment. The biomarker AGRN, serving as a therapeutic target for BC, emerges as a prospective avenue for enhancing both diagnosis and prognosis in BC cases.