It is worthwhile to establish a prognostic prediction model based on microenvironment cells (MCs) infiltration and explore new treatment strategies for triple-negative breast cancer (TNBC).

Overall, our results demonstrate that MCs infiltration can be exploited as a novel indicator for the prognosis and therapeutic regimen selection of the TNBC patients.

The xCell algorithm was used to quantify the cellular components of the TNBC microenvironment based on bulk RNA sequencing (bulk RNA-seq) data. The MCs index (MCI) was constructed using the least absolute shrinkage and selection operator Cox (LASSO-Cox) regression analysis. Single-cell RNA sequencing (scRNA-seq), spatially resolved transcriptomics (SRT), and multiplex immunofluorescence (mIF) staining analyses verified MCI. The mechanism of action of the MCI was investigated in tumor-bearing mice.

MCI consists of the six types of MCs, which can precisely predict the prognosis of the TNBC patients. scRNA-seq, SRT, and mIF analyses verified the existence and proportions of these cells. Furthermore, combined with the spatial distribution characteristics of the six types of MCs, an MCI-enhanced (MCI-e) model was constructed, which could predict the prognosis of the TNBC patients more accurately. More importantly, inhibition of the insulin signaling pathway activated in the cancer cells of the MCIhigh the TNBC patients significantly prolonged the survival time of tumor-bearing mice. Conclusions: Overall, our results demonstrate that MCs infiltration can be exploited as a novel indicator for the prognosis and therapeutic regimen selection of the TNBC patients.