Prospects of Extracellular Vesicles in Otorhinolaryngology, Head and Neck Surgery

The diagnostic and therapeutic potential of extracellular vesicles (EVs) has been recognised in many fields of medicine for several years. More recently, it has become a topic of increasing interest in otorhinolaryngology, head and neck surgery (ORL-HNS). With this narrative review, we have aspired to determine different aspects of those nanometrically sized theranostic particles, which seem to have promising potential as biomarkers in some of the most common diseases of the ORL-HNS by being available via less invasive diagnostic methods. At the same time, a better understanding of their activity provides us with new possibilities for developing specific target treatments. So far, most research has been oriented towards the role of EVs in the progression of head and neck cancer, notably head and neck squamous cell cancer. Nonetheless, some of this research has focused on chronic diseases of the ears, nose and paranasal sinuses. However, most research is still in the preclinical or experimental phase. It therefore requires a further and more profound understanding of EV content and behaviour to utilise their nanotheranostic capacities to their fullest potential.

Associations between dynamic-contrast enhanced MRI and tumor infiltrating lymphocytes and tumor-stroma ratio in head and neck squamous cell cancer

Objectives The present study used dynamic-contrast enhanced MRI (DCE-MRI) to elucidate possible associations with tumor-infiltrating lymphocytes (TIL), stroma ratio and vimentin expression in head and neck squamous cell cancer (HNSCC). Methods Overall, 26 patients with primary HNSCC of different localizations were involved in the study. DCE-MRI was obtained on a 3 T MRI and analyzed with a whole lesion measurement using a histogram approach. TIL- and vimentin-expression was calculated on bioptic samples before any form of treatment. P16 staining was used to define HPV-status. Results Tumor-stroma ratio correlated with entropy derived from Ktrans (r = − 0.52, p = 0.0071) and with kurtosis derived from Ve (r = − 0.53, p = 0.0058). Several Ve derived parameters correlated with expression of TIL within the stroma compartment. TIL within the tumor compartment correlated with entropy derived from Ktrans (r = 0.39, p = 0.047), p90 derived from Ve (r = 0.41, p = 0.036) and skewness derived from Ve (r = 0.41, p = 0.037). Furthermore, these associations were different between HPV positive and negative tumors. Conclusions DCE-MRI might be able to reflect tumor compartments and TIL expression in HNSCC. The most promising parameters were values derived from Ktrans and Ve.

Relationship between Tumor Mutational Burden, PD-L1, Patient Characteristics, and Response to Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma

Failure to predict response to immunotherapy (IO) limited its benefit in the treatment of head and neck squamous cell cancer (HNSCC) to 20% of patients or less. Biomarkers including tumor mutational burden (TMB) and programmed death ligand-1 (PD-L1) were evaluated as predictors of response to IO, but the results are inconsistent and with a lack of standardization of their methods. In this retrospective study, TMB and PD-L1 were measured by commercially available methodologies and were correlated to demographics, outcome, and response to PD-1 inhibitors. No correlation was found between TMB and PD-L1 levels. High TMB was associated with smoking and laryngeal primaries. PD-L1 was significantly higher in African Americans, patients with earlier stage tumors, nonsmokers, and nonethanol drinkers. Patients with high TMB fared better in univariate and multivariate survival analysis. No correlation was found between PD-L1 expression and prognosis. There was a statistically significant association between PFS and response to IO and TMB. There was no association between response to ICI and PD-L1 in this study, possibly affected by variations in the reporting method. Further studies are needed to characterize the biomarkers for IO in HNSCC, and this study supports further research into the advancement of TMB in prospective studies.

Moving towards the Future of Radio-Immunotherapy: Could We “Tailor” the Abscopal Effect on Head and Neck Cancer Patients?

The abscopal effect (AbE) is defined as radiation-induced shrinkage of distant, non-treated, neoplastic lesions and it is considered the best clinical picture of the efficient immune stimulation by irradiation. The first report about abscopal tumor regression upon radiotherapy dates back to the beginning of the 20th century. The growing preclinical and clinical synergism between radiation and immunotherapy gave birth the purpose to more easily reproduce the abscopal effect, nevertheless, it is still rare in clinical practice. In this review we summarize immunological modulation of radiotherapy, focusing on the well-balanced equilibrium of tumor microenvironment and how radio-immunotherapy combinations can perturb it, with particular attention on head and neck squamous cell cancer. Finally, we investigate future perspectives, with the aim to “tailor” the abscopal effect to the patient.