Association of Tumour-Associated Macrophage States with Non-conserved lncRNAs in Lung Cancer

Tumour-associated macrophages (TAMs) are central players in the tumour microenvironment, driving cancer progression and modulating immune responses. Renowned for their ability to rapidly adapt to environmental changes, TAMs can adopt a wide range of functional phenotypes. However, the regulatory mechanisms underlying this functional plasticity are still not fully understood. Long non-coding RNAs (lncRNAs), as key regulators of epigenetic and post-transcriptional processes, are increasingly recognized for their potential role in TAM polarization. In this study, we conducted a comprehensive comparative analysis of lncRNA expression in TAMs derived from both mouse and human lung carcinomas. Although we identified a small group of murine lncRNAs as potential human orthologs through orthogonal in silico approaches, the majority of murine lncRNAs lacked clear human equivalents. Overall, our findings reveal distinct lncRNA expression patterns in lung carcinoma mouse and human TAMs, underscoring the importance of utilizing human-based models to thoroughly investigate the roles of lncRNAs in immune regulation and bridge the translational gap between murine and human cancer immunology. Overall design: MHC-II low and high TAMs were extracted from Lewis lung carcinoma bearing mice.