The regulatory role of long non- coding RNAs as a novel controller of immune response against cancer cells.

Immunotherapy has been established as a promising therapy for different cancer types. However, many patients experience primary or secondary resistance to treatment. Immune cells and anti-inflammatory factors are regulated by long noncoding RNAs (lncRNAs). In addition, lncRNAs have a role in immune resistance through antigen presentation loss or attenuation, PD-L1 upregulation, loss of T-cell activities, and activation of G-MDSCs and Tregs in the tumor environment. LncRNAs can also influence the interaction between cancer stem cells and immune cells in the tumor microenvironment, potentially resulting in cancer stem cell resistance to immunotherapy. Immunological-related lncRNAs can influence immune responses either directly by affecting neighboring protein-coding genes or indirectly by sponging miRNAs through various mechanisms. We have emphasized the role and levels of expression of lncRNAs that have been linked to immune cell formation, differentiation, and activation, which may have an influence on immunotherapy efficacy.