BASP1 drives breast cancer progression and immunosuppression by recruiting MDSCs and suppressing T cells

Myeloid-derived suppressor cells (MDSCs) are critical immunosuppressive components within the tumor microenvironment (TME), significantly influencing breast cancer (BC) development and progression. Current therapeutic strategies often fall short due to the complex interplay between cancer cells and the immune system. Identifying specific genes that modulate MDSC activity is crucial for developing novel, more effective treatments for BC patients by targeting the immunosuppressive TME.

Researchers integrated bulk RNA-seq data from the TCGA-BC cohort with scRNA-seq data from the GSE176078 dataset to identify MDSC-related genes via bioinformatic analysis. They then evaluated the prognostic potential and immune infiltration correlation of the hub gene BASP1 in BC patients. Functional roles of BASP1 were investigated both in vitro using BC cell lines (proliferation, migration assays) and in vivo using mouse models bearing 4T1 tumors. ELISA and flow cytometry were likely used to assess immune cell populations and cytokine levels.

BASP1 levels were significantly higher in BC tissues compared to adjacent normal tissues, and elevated BASP1 expression was closely associated with adverse clinical outcomes. Patients with increased BASP1 levels exhibited increased infiltration of immunosuppressive cells, specifically M2 macrophages and Tregs, while showing reduced infiltration of CD8+ T cells. In vitro, downregulation of BASP1 suppressed BC cell proliferation and migration through inactivation of AKT and ERK signaling pathways. Mechanistically, BASP1 in 4T1 cells promoted MDSC migration, at least partially, via upregulating CXCL12 secretion. Furthermore, BASP1 in MDSCs directly suppressed T cell function. > In vivo experiments demonstrated that BASP1 knockdown markedly inhibited tumor growth in mouse models bearing 4T1 tumors, accompanied by decreased MDSC infiltration and increased Granzyme B+ CD8+ T cell accumulation in tumor tissues.