Tumor Microenvironment Characterization Identifies KIF15 as an Immunosuppressive Driver in Breast Cancer

The various cellular composition of the tumor microenvironment (TME) comprises the fundamental units of tumor tissue. The types of stromal cells in the TME are genetically stable, with reduced risk of tumor recurrence and drug resistance. More and more evidence shows their clinicopathological significance and therapeutic effect in predicting prognosis. Therefore, we performed an integrated analysis of the breast cancer TME, correlating it with genomic landscapes and clinical profiles. In this work, we first conducted unsupervised hierarchical clustering on 830 tumors in the breast cancer cohort. Then, we defined three TME phenotypes and applied principal component analysis to construct a TMEscore for quantifying TME. Analysis revealed that patients stratified into the high TMEscore cohort exhibited superior survival compared to the low‐scoring group. Additionally, a high TMEscore is associated with an improved response to immunotherapy. Through TME gene signature analysis, KIF15 was identified as a pivotal driver of the immunosuppressive microenvironment in breast cancer. KIF15 knockdown may promote dendritic cell infiltration and function, thereby inducing CD8 + T cell recruitment. In summary, the immune microenvironment‐derived TMEscore represents an independent prognostic biomarker in breast cancer, while KIF15 emerges as a crucial molecular determinant of its immunosuppressive niche.