CD24a knockout transforms the tumor microenvironment from cold to hot by promoting tumor-killing immune cell infiltration in a murine triple-negative breast cancer model
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Background
CD24 plays a crucial role not only in promoting tumor progression and metastasis but also in modulating macrophage-mediated anti-tumor immunity. However, the impact of tumor CD24 on the immune landscape of the tumor microenvironment (TME) remains poorly explored. Here, we investigated the role of CD24a, murine CD24 gene, in the progression and immune dynamics of the tumor microenvironment (TME) in the 4T1 murine model of triple-negative breast cancer (TNBC). Methods: We employed Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 technology to perform a gene knockout of Cd24a in 4T1 cells. Flow cytometry was utilized to analyze the distribution and number of immune cells, including myeloid-derived suppressor cells (MDSCs), natural killer (NK) cells, T cells, and macrophages, within tumors, spleens, and bone marrow. Immunofluorescence (IF) staining was used to detect these immune cells in tumor sections. Additionally, ANDOR Dragonfly High-Speed Confocal was used to perform three-dimensional (3D) mapping of mouse tumors.
Results
Our study showed that knocking out CD24a significantly impeded tumor progression and prolonged mouse survival. Flow cytometry and IF analysis revealed that the loss of CD24a transformed tumor microenvironment from cold to hot by promoting the infiltration of M1 macrophages, cytotoxic CD8 + T cells, and CD49b + natural killer (NK) cells while reducing the recruitment and expansion of granulocytic myeloid-derived suppressor cells (gMDSCs) in the TME. Additionally, the 3D mapping of TME further validated the “hot state” of CD24a knockout tumors.
Conclusions
Our study provides the first evidence that targeting CD24a could effectively reprogram the TME, enhancing its immunogenicity, and transforming immune cold tumors into hot tumors. This strategy may offer a promising therapeutic strategy for enhancing the immune response against poorly immunogenic tumors.
