Figure 5.

LncRNAs-regulated resistance to immunotherapy. In BC cells, LINK-A promotes the crosstalk between PIP3 and inhibitory GPCR pathways, leading to decreased cAMP and PKA-mediated phosphorylation of TRIM71. Decreased phosphorylation of TRIM71 enhances the degradation of PLC, Rb and p53, resulting in downregulation of antigenicity and intrinsic tumor resistance to immunotherapy. In stimulated T cells, calcium influx activates calmodulin, thereby removing HDAC and enhancing STAT1-mediated transcription of NKILA. NKILA directly binds to p65 and prevents its nuclear translocation as well as following transcription of anti-apoptotic genes. Thus, NKILA facilitates T cell vulnerability to AICD, resulting in immune evasion and cancer progression of BC.