Immune cell lncRNAs reprogram the tumor microenvironment

Area of Science:

• Immunology
• Molecular Biology
• Cancer Research

Background:

• Long noncoding RNAs (lncRNAs) are recognized regulators of the tumor microenvironment (TME).
• Their specific roles within immune cells of the TME are often overlooked.
• This review focuses on the cell-intrinsic functions of lncRNAs in immune populations.

Purpose of the Study:

• To systematically review the cell-intrinsic roles of lncRNAs in key immune cell types within the TME.
• To highlight lncRNAs acting as molecular switches in immune cell states.
• To explore the potential of lncRNAs as biomarkers and therapeutic targets in immuno-oncology.

Main Methods:

• Systematic literature review of immune cell-intrinsic lncRNAs.
• Analysis of lncRNA regulation in CD8+ T cell exhaustion, CD4+ T cell polarization, NK cell cytotoxicity, dendritic cell antigen presentation, and macrophage programming.
• Examination of exosomal lncRNA functions.

Main Results:

• Immune cell-intrinsic lncRNAs critically govern T cell exhaustion and polarization, NK cell function, antigen presentation, and macrophage inflammatory responses.
• Certain lncRNAs act as molecular switches, modulating immune cells between antitumor and immunosuppressive states.
• Exosomal lncRNAs mediate intercellular communication within the TME.

Conclusions:

• Immune cell-intrinsic lncRNAs are crucial regulators of immune cell function within the TME.
• Targeting these lncRNAs presents opportunities for novel cancer biomarkers and therapies.
• Integrating lncRNA biology into precision immuno-oncology is a promising future direction.