Suppression of lymphocyte functions by plasma exosomes correlates with disease activity in patients with head and neck cancer

Purpose: Head and neck cancers (HNC) often induce profound immunosuppression which contributes to disease progression and interferes with immune-based therapies. Body fluids of HNC patients are enriched in exosomes potentially engaged in negative regulation of anti-tumor immune responses. The presence and content of exosomes derived from plasma of HNC patients are evaluated for the ability to induce immune dysfunction and influence disease activity. <p>Experimental Design: Exosomes were isolated by size-exclusion chromatography from plasma of 38 HNC patients and 14 healthy donors. Morphology, size, numbers and protein and molecular contents of the recovered exosomes were determined. Co-culture assays were performed to measure exosome-mediated effects on functions of normal human lymphocyte subsets and natural killer (NK) cells. The results were correlated with disease stage and activity.</p> <p>Results: The presence, quantity and molecular content of isolated, plasma-derived exosomes discriminated HNC patients with active disease (AD) from those with no evident disease (NED) after oncological therapies. Exosomes of patients with AD were significantly more effective than exosomes of patients with NED in inducing apoptosis of CD8⁺ T cells, suppression of CD4⁺ T cell proliferation and up-regulation of regulatory T cell (Treg) suppressor functions (all at p < 0.05). Exosomes of AD patients also down-regulated NKG2D expression levels in NK cells.</p> Conclusions: Exosomes in plasma of HNC patients carry immunosuppressive molecules and interfere with functions of immune cells. Exosome-induced immune suppression correlates with disease activity in HNC, suggesting that plasma exosomes could be useful as biomarkers of HNC progression.

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