Immune cell lncRNAs reprogram the tumor microenvironment

Long noncoding RNAs (lncRNAs) regulate the tumor microenvironment (TME), yet their cell-intrinsic roles within immune populations of the TME remain underappreciated. In this review, we shift focus from the cancer cell to the immune compartment, systematically reviewing how immune cell-intrinsic lncRNAs govern CD8⁺ T cell exhaustion, CD4⁺ T cell polarization, NK cell cytotoxicity, dendritic cell antigen presentation, and macrophage inflammatory programming. We highlight lncRNAs that function as molecular switches-tipping immune cells between antitumor effector and immunosuppressive states-and examine how exosomal lncRNAs extend these regulatory circuits across cellular boundaries within the TME. Finally, we evaluate opportunities for lncRNA-based biomarkers and therapies designed to target the immune landscape, outlining a framework for integrating immune-intrinsic lncRNA biology into precision immuno-oncology.