Pan-cancer integrative profiling of immune-related lncRNAs unveils tumor microenvironment subtypes and prognostic biomarkers

Long non-coding RNAs (lncRNAs) have been widely implicated in modulating immune pathway activity and immune cell infiltration to influence cancer outcomes. However, only a few immune-related lncRNAs have been shown to play significant roles in cancer progression. Therefore, we propose an algorithm, LncImmune, to identify immune cell related-lncRNAs, and integrate existing algorithms to comprehensively reveal candidate lncRNA regulators involved in immune pathways in specific immune cells across 32 cancer types. We demonstrated that immune cell-related lncRNAs exhibit expression perturbations in cancer and respond actively to immune pathway activity. The integrated algorithm further delineated the immune regulatory features of lncRNAs, revealing their tumor-associated roles. Utilizing core lncRNA regulators, we identified two molecular subtypes of lung adenocarcinoma, (C1 and C2 termed the “cold” and “hot” immune phenotypes, respectively), which were distinguished by divergent genetic mutation landscapes, immune cell infiltration levels, immune checkpoint expression profiles, inferred drug sensitivities, and prognostic outcomes. In conclusion, the LncImmune serves as an important method in exploring the functional role of lncRNA in tumor immunity, which would shed light on the development of potential carcinogenic biomarkers and immunotherapeutic targets.