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.