Regulatory and Physiological Roles of lncRNAs in Tumor Immunotherapy Response

Immunotherapy harnesses the patient’s immune system to recognize and eliminate malignant cells and constitutes the forefront of cancer therapies. Notwithstanding, intrinsic and acquired immunotherapy resistance mechanisms operating within the tumor microenvironment remain a limitation to achieving durable and effective clinical responses. Long noncoding RNAs (lncRNAs) emerge as critical regulators of gene expression both in tumor and immune cells, modulating processes that affect resistance to immunotherapy response, including T-cell differentiation, macrophage polarization, dendritic cell maturation, and cytokine signaling. Their tissue-specific expression and regulatory roles in the physiology of the tumor immune microenvironment and response to immune checkpoint inhibitors make them attractive molecules to search for predictive biomarkers and targets for combined RNA-based interventions that improve immunotherapy response.