MiR-9 promotes G-MDSC recruitment and tumor proliferation by targeting SOCS3 in breast cancer.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of cells that differentiate from myeloid cells, proliferate in cancer and inflammatory reactions, and mainly exert immunosuppressive functions. Nonetheless, the precise mechanisms that dictate both the accumulation and function of MDSCs remain only partially elucidated. In the course of our investigation, we observed a positive correlation between the content of MDSCs especially G-MDSCs and miR-9 level in the tumor tissues derived from miR-9 knockout MMTV-PyMT mice and 4T1 tumor-bearing mice with miR-9 overexpression. Combined with RNA-seq analysis, we identified SOCS2 and SOCS3 as direct targets of miR-9. Additionally, our research unveiled the pivotal role of the CCL5/CCR5 axis in orchestrating the chemotactic recruitment of G-MDSCs within the tumor microenvironment, a process that is enhanced by miR-9. These findings provide fresh insights into the molecular mechanisms governing the accumulation of MDSCs within the framework of breast cancer development.

CD38 and extracellular NAD+ regulate the development and maintenance of Hp vaccine-induced CD4+ TRM in the gastric epithelium.

Tissue-resident memory T cells (TRM) can be induced by infection and vaccination, and play a key role in maintaining long-term protective immunity against mucosal pathogens. Our studies explored the key factors and mechanisms affecting the differentiation, maturation, and stable residence of gastric epithelial CD4+ TRM induced by Helicobacter pylori (Hp) vaccine and optimized Hp vaccination to promote the generation and residence of TRM. Cluster of differentiation (CD)38 regulated mitochondrial activity and enhanced transforming growth factor-ß signal transduction to promote the differentiation and residence of gastric epithelial CD4+ TRM by mediating the expression of CD105. Extracellular nucleotides influenced the long-term maintenance of TRM in gastric epithelium by the P2X7 receptor (P2RX7). Vitamin D3 and Gram-positive enhancer matrix (GEM) particles as immune adjuvants combined with Hp vaccination promoted the production of CD69+CD103+CD4+ TRM.