# Differential effects of small extracellular vesicles from head and neck cancer patients on dendritic cell functions

## TL;DR

This study explores how small extracellular vesicles from head and neck cancer patients affect dendritic cell functions, revealing both direct and systemic immune-modulating effects.

## Contribution

The study reveals novel mechanisms by which tumor-derived extracellular vesicles modulate dendritic cell maturation and antigen presentation in head and neck cancer.

## Key findings

- Vesicles from HPV(+) tumor cells increased maturation and activation of immature dendritic cells.
- Immature dendritic cells co-incubated with vesicles showed reduced antigen presentation and IL12p70 production.
- Patient-derived vesicles inhibited mature dendritic cell functions by downregulating antigen presenting machinery.

## Abstract

Tumor-derived small extracellular vesicles were shown to contribute to immunosuppression in various cancer types, including head and neck squamous cell carcinoma. Dendritic cells, major regulators of specific anti-tumor immune response, are often impaired in their function in the context of cancer.

Monocyte-derived dendritic cells were incubated with isolated small extracellular vesicles during or after maturation. Cell surface markers and antigen processing machinery were assessed by flow cytometry. Vesicle-treated dendritic cells were tested for interleukin 12p70 production by ELISA, and differences in uptake of labeled vesicles were shown by confocal microscopy.

Small extracellular vesicles derived from HPV(+) tumor cell lines increased maturation and activation of immature dendritic cells, priming them for more rapid phagocytosis. Immature dendritic cells co-incubated with vesicles had lower levels of antigen presenting machinery components and produced less IL12p70 than controls, while similarly co-incubated mature dendritic cells remained unaffected. Vesicles in plasma of patients with head and neck cancer inhibited functions of mature dendritic cells by downregulating expression of antigen presenting machinery components.

Our results uncover mechanisms through which tumor-derived small extracellular vesicles modulate dendritic cell functions locally and systemically. These mechanisms may also affect dendritic cell-based vaccine efficacy.

Diagram showing direct and systemic effects on dendritic cells (DCs). In the direct effect, TEX increases maturation and activation of immature DCs, while mature DCs show no effect. In the systemic effect, HNSCC plasma sEVs increase CCR7 expression in immature DCs and decrease APM components in mature DCs.