Work

VAMP4/STX8 Mediate the Autophagic Secretion of Mitochondria and Promote TAMs Polarization in HNSCC

Year: 2026

Type: article

Abstract: Under hypoxic conditions, tumour cells engage in autophagic secretion of mitochondria to sustain energy balance and modulate the tumour microenvironment. However, the exact molecular mechanisms remain unclear. This study used a combination of multivesicular bodies membrane proteomics and molecular interaction validation to demonstrate that hypoxia promotes mitophagy-dependent extracellular vesicles (EVs) secretion in head and neck squamous cell carcinoma (HNSCC). This process promotes tumour-associated macrophages to adopt immunosuppressive phenotypes, reshaping the immune environment. Vesicle-associated membrane protein 4 (VAMP4) and syntaxin 8 (STX8) are key molecules involved in this secretion. Clinically, VAMP4/STX8 expressions are significantly higher in HNSCC than in normal tissues and correlate with prognosis, indicating their potential as biomarkers and therapeutic targets. This study revealed the mitophagy-secretion axis that reshaped the tumour immune landscape, providing a theoretical basis for targeting soluble NSF attachment protein receptor-dependent EV release to enhance the therapeutic effect of HNSCC immunotherapy.

Source: Journal of Extracellular Vesicles

DOI: 10.1002/jev2.70276