Shyam Kishore

Oral Squamous Cell Carcinoma (OSCC) remains a significant public health challenge, characterized by late-stage diagnosis, high recurrence rates, and limited treatment responsiveness. Beyond the primary tumor burden, OSCC progression is influenced by systemic alterations, including inflammation, immune modulation, and metabolic dysregulation. Recent evidence suggests that tumor-derived large extracellular vesicles (LEVs), circulating mitochondria, and cell-free DNA (ccfDNA) play critical roles in shaping the tumor microenvironment and driving disease progression. LEVs, shed in abundance by tumor cells, carry bioactive cargo, such as proteins, nucleic acids, and mitochondrial components, that influence intercellular communication, promote epithelial-mesenchymal transition (EMT), and facilitate immune evasion. Simultaneously, circulating mitochondria and mitochondrial DNA (mtDNA) have emerged as key mediators of systemic inflammation. In OSCC, elevated levels of fragmented ccfDNA, both nuclear and mitochondrial origin, have been associated with increased tumor burden and poorer prognosis. The interplay between LEV cargo, circulating mitochondrial signatures, and ccfDNA-driven immune activation represents a crucial pathophysiological interface in OSCC biology. Understanding this interaction may enable the development of integrated diagnostic biomarkers and precision therapeutic strategies, ultimately improving early detection, treatment outcomes, and survival in OSCC patients.