Landscape of tumor and immune system cells-derived exosomes in lung cancer: mediators of antitumor immunity regulation.

The immune system plays a critical role in cancer, including lung cancer, which is the leading cause of cancer-related deaths worldwide. Immunotherapy, particularly immune checkpoint blockade, has revolutionized the treatment of lung cancer, but a large subset of patients either do not respond or develop resistance. Exosomes, essential mediators of cell-to-cell communication, exert a profound influence on the tumor microenvironment and the interplay between cancer and the immune system. This review focuses on the role of tumor-derived exosomes and immune cells-derived exosomes in the crosstalk between these cell types, influencing the initiation and progression of lung cancer. Depending on their cell of origin and microenvironment, exosomes can contain immunosuppressive or immunostimulatory molecules that can either promote or inhibit tumor growth, thus playing a dual role in the disease. Furthermore, the use of exosomes in lung cancer immunotherapy is discussed. Their potential applications as cell-free vaccines and drug delivery systems make them an attractive option for lung cancer treatment. Additionally, exosomal proteins and RNAs emerge as promising biomarkers that could be employed for the prediction, diagnosis, prognosis and monitoring of the disease. In summary, this review assesses the relationship between exosomes, lung cancer, and the immune system, shedding light on their potential clinical applications and future perspectives.

Aberrant Methylation of the Imprinted C19MC and MIR371-3 Clusters in Patients with Non-Small Cell Lung Cancer.

Epigenetic mechanisms have emerged as an important contributor to tumor development through the modulation of gene expression. Our objective was to identify the methylation profile of the imprinted C19MC and MIR371-3 clusters in patients with non-small cell lung cancer (NSCLC) and to find their potential target genes, as well as to study their prognostic role. DNA methylation status was analyzed in a NSCLC patient cohort (n = 47) and compared with a control cohort including COPD patients and non-COPD subjects (n = 23) using the Illumina Infinium Human Methylation 450 BeadChip. Hypomethylation of miRNAs located on chromosome 19q13.42 was found to be specific for tumor tissue. We then identified the target mRNA-miRNA regulatory network for the components of the C19MC and MIR371-3 clusters using the miRTargetLink 2.0 Human tool. The correlations of miRNA-target mRNA expression from primary lung tumors were analyzed using the CancerMIRNome tool. From those negative correlations identified, we found that a lower expression of 5 of the target genes (FOXF2, KLF13, MICA, TCEAL1 and TGFBR2) was significantly associated with poor overall survival. Taken together, this study demonstrates that the imprinted C19MC and MIR371-3 miRNA clusters undergo polycistronic epigenetic regulation leading to deregulation of important and common target genes with potential prognostic value in lung cancer.