Long non-coding RNAs as key orchestrators of the tumor microenvironment in lung cancer.

Long non-coding RNAs (lncRNAs) are emerging as master regulators of the lung cancer tumor microenvironment (TME), where they reprogram immune cell functions, cytokine networks, and checkpoint signaling to create an immunosuppressive and therapy-resistant landscape. This review offers a comprehensive analysis of how lncRNAs mediate the interplay between tumor cells and immune components, underscoring their context-dependent roles as both oncogenic drivers and microenvironmental suppressors. It also highlights their clinical utility as liquid-biopsy biomarkers and their central role in conferring resistance to chemo- and radio-therapy. This review synthesizes current knowledge on the interplay between lncRNAs and the TME, highlighting the targeting of specific lncRNAs as a novel therapeutic strategy for precision lung cancer therapy.