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Updated: Sep 28, 2026
In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
Published on: September 23, 2021
Small extracellular vesicles from the plasma of head and neck cancer patients induce dysfunctional T cell phenotypes
Luisa Tengler1, Edwin K Jackson2, Karen Bieback3
1Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. luisa.tengler@medma.uni-heidelberg.de.
Background:
Head and neck cancer (HNC) is highly immunosuppressive. Despite advances with immune checkpoint (IC) inhibitors, many HNC patients fail to respond. Tumour-derived small extracellular vesicles (sEVs) may contribute to immune evasion and therapy resistance, possibly by altering T-cell phenotypes.
Method:
Plasma sEVs were isolated from HNC patient samples and controls via size-exclusion chromatography. The plasma sEVs were characterised and analysed for their effects on CD4⁺ and CD8⁺ T-cell function, IC levels and gene expression.
Results:
HNC patient-derived sEVs inhibit CD4+ and CD8+ T-cell function and promote CD8+ T-cell apoptosis, correlating with disease progression. Plasma sEVs can enhance the conversion of ATP to AMP and modulate the expression of ectonucleotidases. IC profiling revealed complex alterations, with CD4⁺ T cells showing increased TIGIT and CTLA-4 but decreased BTLA, PD-1, and LAG-3 expression, whereas CD8⁺ T cells showed a downregulation of both inhibitory and stimulatory ICs. PD-1 blockade did not completely prevent sEV-mediated T-cell suppression.
Conclusions:
Our findings suggest that plasma sEVs contribute to systemic immune modulation in HNC by inducing dysfunctional T-cell phenotypes. The ability of plasma-derived sEVs to modulate IC expression on T cells underscores the need for further investigation into their relevance for immunotherapeutic strategies in HNC.
