TUMOR-DERIVED MICROVESICLES IN SERA OF PATIENTS WITH HEAD AND NECK CANCER AND THEIR ROLE IN TUMOR PROGRESSION

Background. Tumor-derived membranous vesicles (MV) isolated from sera of the patients with squamous cell carcinomas of the head and neck (HNSCC) induce apoptosis of activated CD8(+) T cells. We tested if MV molecular profile and activity correlate with disease progression. Methods. CD8(+) Jurkat cells were incubated with MAGE 3/6(+), FasL(+), MHC class 1(+) MV isolated from sera of 60 patients with HNSCC and 25 normal controls by exclusion chromatography and ultracentrifugation. Z-VAD-FITC binding to Jurkat was measured and correlated with clinical data. Results. MV from patients' sera, but not from sera of normal controls, induced Jurkat cell apoptosis. Forty-five percent T cells+MV from patients with N-1-N-3 disease were apoptotic versus 18% T cells+ MV from patients with N-o disease (p < .008). MV from patients with active disease (AD) expressed higher FasL levels than MV from patients with no evident disease (NED) or normal controls (P <= .01). Conclusion. MAGE 3/6(+), FasL(+), and MHCI+ MV in sera of patients induced T-cell apoptosis, which correlated with disease activity and the presence of lymph node metastases. (C) 2008 Wiley Periodicals, Inc. Head Neck 31: 371-380, 2009