Single-cell sequencing exposes mast cell-derived CD52's anti-tumor action in breast cancer through the IL-6/JAK/STAT3 axis

The aggressive nature and rapid progression of triple-negative breast cancer (TNBC), coupled with a high likelihood of recurrence and mortality, underscore the critical need for effective treatments. While immunotherapy presents promising advantages for those with triple-negative breast cancer (TNBC), its efficacy is not universal. This disparity highlights the importance of investigating survival outcomes and prognostic factors for those TNBC patients who don't respond well to immunotherapy. Our study leverages both bulk and single-cell RNA sequencing data to conduct an in-depth analysis, revealing that genes associated with mast cells (PCMT1, VDAC1, YWHAB, BRD4, BTG1, and CD52) are pivotal in prognostication for TNBC patients. Laboratory experiments have further substantiated our findings, demonstrating that the overexpression of CD52 in mast cells impedes the proliferation, invasion, and metastasis of breast cancer cells. Further anti-CD52 treatment inhibiting breast tumor growth in vivo. Additionally, we have discovered that CD52 elicits its antitumor effects by meditating the IL-6/JAK/STAT3 signaling pathway. These insights not only enhance the prognostic significance of mast cells in TNBC but also pave the way for the development of novel targeted immunotherapy strategies.