Fig. 2

Cancer-derived miRNAs regulate immune evasion via modulating the expression profiles within cancer cells. Firstly, some immune modulatory miRNAs disturb antigen processing and presentation by targeting one or multiple components of APM (e.g., TAP1, LMP8, LMP9, and LMP10) and MHC-I molecules in cancer cells. Secondly, the loss of some HLA-G-targeting miRNAs is highly related with increased HLA-G expression, which is a well-accepted immune tolerant moelcule. Thirdly, cancer cells could escape immune attack by downregulating NKG2D ligands (MICA/B and ULBP2) in post-transcriptional level. Increased MICA/B- or ULBP2-targeting miRNAs protect cancer cells from immune clearence of NKs and CTLs. Fourthly, altered miRNA expressio pattern upregulates PD-L1 level in cancer cells. Lastly, dysregulated miRNA profiles change the metabolism of cancer cells. Increased IDO1 further hampered the normal immune survelliance. The miRNAs promoting anti-cancer immune response are exihibited in boxes with green background while the miRNAs inhbiting anti-cancer immune reponse are showed in boxes with red background. Upregualted immunostiumlatory miRNAs together with downregualted immunosuppressive miRNAs contribute to cancer immune evasion. APM antigen processing machinery, TAP transporter associated with antigen processing, MHC-I major histocompatibility complex class I, LMP proteasome subunits latent membrane protein, MICA/B MHC-I chain-related molecules A/B, ULBP UL16-binding protein, CTL cytotoxic T lymphocyte, IDO indoleamine 2, 3-dioxygenase