LINC01929 mediates breast cancer immunosuppression and is an immunotherapy target

To identify long non-coding RNAs (lncRNAs) involved in breast cancer immunosuppression, we analyzed lncRNA expression and their correlation with tumor-infiltrating lymphocytes, association with worse patient outcomes, and enrichment in breast cancer and identified LINC01929 was a top hit in breast and other cancer types. Knockdown of LINC01929 in breast cancer cell lines reduced cell survival, cell cycle progression, inhibited tumor growth, and altered the expression of genes involved in growth, immune, and antigen presentation pathways. LINC01929 acts as a competitive endogenous RNA, regulating a cancer-promoting and immunosuppressive microRNA-mRNA network. Targeting LINC01929 in breast cancer cells increases proteasomal activity, and cell surface levels of human leukocyte antigen calls I (HLA I) and programmed death-ligand 1 (PD-L1). In breast tumors, LINC01929 expression negatively correlated with T cell abundance. Targeting LINC01929 sensitized breast cancer cells to activated T cell killing. These findings identify LINC01929 as an immunotherapy target to overturn breast cancer immunosuppression.