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<p>Myeloid-derived suppressor cells (MDSCs) are essential immunosuppressive elements found within the tumor microenvironment (TME) and significantly influence the development of breast cancer (BC). Given their critical role in cancer progression, identifying MDSC-related genes is urgently needed to develop more effective treatment strategies for BC patients. The integration of bulk RNA-seq data from the TCGA-BC cohort alongside scRNA-seq data from the GSE176078 dataset was performed for identifying MDSC-related genes through bioinformatic analysis. Subsequently, the potential of the hub gene BASP1 in predicting prognosis and immune infiltration in BC was evaluated. Furthermore, the functional role of BASP1 in BC was investigated both in vitro and in vivo. Notably, BASP1 levels were significantly higher in BC tissues than in adjacent normal tissues, and elevated BASP1 expression was closely associated with adverse clinical outcomes. Additionally, BC patients with increased BASP1 levels exhibited increased infiltration of immunosuppressive cells (M2 macrophages and Tregs) but reduced infiltration of CD8 + T cells. Functionally, downregulation of BASP1 was observed to suppress BC cell proliferation and migration in vitro through inactivation of AKT and ERK signalings. Mechanistically, BASP1 in 4T1 cells promoted MDSC migration, at least partially, via upregulating CXCL12 secretion, while BASP1 in MDSCs directly suppressed T cell function. In vivo experiments showed that BASP1 knockdown markedly inhibited tumor growth in mouse models bearing 4T1 tumors, accompanied by decreased MDSCs infiltration and increased Granzyme B + CD8 + T cell accumulation in tumor tissues. Collectively, BASP1 may serve as a potential prognostic biomarker and a therapeutic target for BC intervention, functioning both as a pro-tumorigenic gene and as an immunomodulatory molecule that shapes an immunosuppressive microenvironment.</p>

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BASP1 promotes breast cancer progression and shapes an immunosuppressive microenvironment by recruiting MDSCs and suppressing T cell function

  • 期刊论文

  • 发表日期：

    2026年6月23日

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  • Haijie Hu,
  • Xiaomin Feng,
  • Zhi’an Yan,
  • Fuzhong Qi,
  • Donghai Li,
  • Xuegang Luo

摘要

Myeloid-derived suppressor cells (MDSCs) are essential immunosuppressive elements found within the tumor microenvironment (TME) and significantly influence the development of breast cancer (BC). Given their critical role in cancer progression, identifying MDSC-related genes is urgently needed to develop more effective treatment strategies for BC patients. The integration of bulk RNA-seq data from the TCGA-BC cohort alongside scRNA-seq data from the GSE176078 dataset was performed for identifying MDSC-related genes through bioinformatic analysis. Subsequently, the potential of the hub gene BASP1 in predicting prognosis and immune infiltration in BC was evaluated. Furthermore, the functional role of BASP1 in BC was investigated both in vitro and in vivo. Notably, BASP1 levels were significantly higher in BC tissues than in adjacent normal tissues, and elevated BASP1 expression was closely associated with adverse clinical outcomes. Additionally, BC patients with increased BASP1 levels exhibited increased infiltration of immunosuppressive cells (M2 macrophages and Tregs) but reduced infiltration of CD8 + T cells. Functionally, downregulation of BASP1 was observed to suppress BC cell proliferation and migration in vitro through inactivation of AKT and ERK signalings. Mechanistically, BASP1 in 4T1 cells promoted MDSC migration, at least partially, via upregulating CXCL12 secretion, while BASP1 in MDSCs directly suppressed T cell function. In vivo experiments showed that BASP1 knockdown markedly inhibited tumor growth in mouse models bearing 4T1 tumors, accompanied by decreased MDSCs infiltration and increased Granzyme B + CD8 + T cell accumulation in tumor tissues. Collectively, BASP1 may serve as a potential prognostic biomarker and a therapeutic target for BC intervention, functioning both as a pro-tumorigenic gene and as an immunomodulatory molecule that shapes an immunosuppressive microenvironment.