Tumor Immunology

Exosomes and Head and Neck Cancer

  

Hhuman tumors utilize various mechanisms to evade the immune system and protect themselves from tumor-induced immune suppression. Among the broad variety of mechanisms contributing to immune suppression in the tumor microenvironment (TME), more recent studies have identified nanosized extracellular vesicles (exosomes) as carriers of immunosuppressive proteins that upon delivery to recipient immune cells re-program their functions, inducing suppression of anti-tumor activities.  Exosomes serve as an effective communication system between the tumor and the host cells. Human tumors, including head and neck squamous cell carcinomas (HNSCCs), produce large quantities of exosomes referred to as TEX, and plasma of patients with HNSCC contains significantly more exosomes than plasma of healthy donors. Further, plasma levels of total exosomes have a prognostic value and have been linked to overall survival in patients with melanoma and to disease activity as well as stage in HNSCC. Hence, exosomes have the potential to serve as liquid biomarkers of immune activity and tumor stage.

Modulation of the Tumor Mikroenvironment

Presence of cytotoxic CD8+ T cells (CTLs) in tumor microenvironments (TME) is critical for the effectiveness of immune therapies, while intratumoral regulatory T(reg) cells and myeloid-derived suppressor cells (MDSC) facilitate cancer progression. Toll-like receptor (TLR) ligands all induce both CTL-attractants and Treg/MDSC attractants and suppressive factors, raising the question of whether their induction can be separated for enhanced immunostimulatory action. Using human whole tumor explants and cell cultures we evaluate the interplay between TLR ligands and other immune stimulants as IFN alpha and COX-2 inhibitors in order to modulate the TMR towards a more effective anti-tumor immunity

Photodynamic Therapy


Photodynamic therapy (PDT) represents a palliative treatment option for a selected group of patients with head and neck squamous cell carcinoma (HNSCC). PDT induces a local inflammatory reaction with the potential to initiate antitumor immune responses. Despite the fact that PDT is a local treatment regiment in patients with cancer-induced immune suppression, a PDT mediated systemic inflammatory reaction is visible.  Even more, a  PDT-mediated conversion from mesenchymal to epithelial tumor phenotype was mediated by exosomes, which also serve as non-invasive biomarkers of this transition.     

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