However, miRNA candidates are based on modified nucleic acids and therefore still present delivery challenges in clinical applications.41 In contrast, SAHA and VPA are HDACis that have already been used in clinical scenarios. The present results revealed that treating BC cells with HDACis effectively sensitized tumor cells to NK cell recognition (Figure 6f). HDACis increase the expression of NKG2DLs in myeloma25 and colon cancer cells.42 In this study, we demonstrated that in BC cells, HDACis upregulated the expression of not only MICA/B but also ULBP2. This upregulation of NKG2DLs is typically accompanied by a decrease in the expression of miR-17-92 members (Figure 6d). The HDACi-induced overexpression of MICA/B and ULBP2 was reversed with a miR-20a mimic (Figure 6e). Previous study reported that HDACis butyrate, SAHA and VPA inhibited miR-17-92 transcription by reducing c-Myc expression.42 However, H Yang et al.43 proposed that SAHA downregulated the miR-17-92 cluster by abolishing tyrosine phosphorylation of STAT3 and decreased MCM7 transcription. Thus, the mechanisms for how HDACis downregulate the expression of miR-17-92 require further observation. In addition, we found that SAHA and VPA did not effectively elevate the NKG2DL expression of the normal breast cell line HBL-100 (Figure 6c). The basis for normal breast cell resistance to HDACis is not fully understood, although cancer cells with multiple defects cannot reverse the critical effects of HDACis similar to normal cells.44, 45 This resistance of normal breast cells presumably functions to avoid the autoimmunity caused by treatment with HDACis. Taken together, our study indicates that BC patients who receive HDACi treatment might show increased immune activation in addition to tumor cell inhibition.