Exosome DNA: Critical regulator of tumor immunity and a diagnostic biomarker

Nanosized cellular vesicles “exosome” contains a variety of biological cargo including DNA fragments from cell-of-origin. Despite its biological stability and clinical utility in tumor diagnosis, exosome DNA (ExoDNA) is very little studied as compare with exosome RNA. Cytoplasmic accumulation of damaged DNA from nucleus and mitochondria often leads to its packaging in exosomes by yet unknown pathways. ExoDNA modulates tumor immunity via paracrine interactions and activation of cytosolic DNA sensor pathways, for example, STING, cGAS, and so forth in specific immune cell subsets. In addition to priming tumor immunity, ExoDNA is also emerging as a critical regulator of check-point immunotherapy. As a useful diagnostic biomaterial, ExoDNA contains a variety of clinically relevant tumor-specific mutations representing multiple genes (e.g., EGFR, BRAF, RAS, IDH, and HER2), thus making it a promising “liquid biopsy” material for therapy recommendations. Hence, ExoDNA in addition to tumor immunity modulation, is also emerging as a suitable diagnostic material for personalized therapy in cancer. Here, we review the current status of ExoDNA research and its potential uses in tumor biology.