Anti-programmed death-1 (PD-1) receptor-based therapeutics improve survival in patients with recurrent head and neck squamous cell carcinoma (HNSCC), but many do not benefit due to a low response rate.
Programmed cell death-1 (PD-1) pathway inhibition in head and neck squamous cell carcinoma (HNSCC) has demonstrated inconsistent efficacy regarding human papillomavirus (HPV) status and PD-L1 expression.
This work provides evidence that HPV status can be used to predict the effectiveness of PD-1 inhibitors in HNSCC, independently of PD-L1 expression and TMB, and probably results from an inflamed immune microenvironment induced by HPV infection.
Over the past few years immune checkpoint inhibitors (ICI) targeting cytotoxic lymphocyte antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1) have changed treatment paradigms in many malignancies and are currently under investigation in HNSCC as well.
Investigation of immune checkpoint inhibitors (ICI), such as antibodies targeting programmed cell death protein 1 (PD-1) and its ligand PD-L1, resulted in a change of paradigms in oncology and in the first approval of new drugs for treating SCCHN.
OX40L and PDGFRB overexpression was associated with poor outcomes, whereas PD-1 overexpression was associated with good prognosis in patients with HNSCC treated with primary surgery, suggesting their relevance as potential prognostic biomarkers and major therapeutic targets.
Programmed cell death protein 1 (PD-1) inhibitors have efficacy in treating squamous cell carcinoma of the head and neck (SCCHN), but objective response rates are low.
<b>Introduction:</b> T cell checkpoint inhibitors targeting Programmed cell Death protein-1 (PD-1) have emerged as novel immunotherapy agents showing remarkable efficacy in head and neck squamous cell carcinoma (HNSCC).
Pembrolizumab is an anti-programmed death 1 (PD-1) receptor monoclonal antibody that has shown activity as second line treatment for metastatic head and neck squamous cell carcinoma (HNSCC).
In the present study, we investigated the expression and significance of high mobility group box 1 (HMGB1), HMG nucleosome-binding protein 1 (HMGN1), the receptor programmed cell death 1 (PD-1) and its ligand programmed cell death ligand 1 (PD-L1) in head and neck squamous cell carcinoma (HNSCC).
Immune therapies, in particular those targeting the PD1 receptor or its ligand PD-L1, including nivolumab, pembrolizumab, durvalumab, and atezolizumab have shown significant efficacy in subsets of patients with HNSCC.
For all patients, PD-1 expression on CD8<sup>+</sup> T cells - particularly in HPV-negative HNSCC cases - strongly correlated (r = 0.63, P = 0.013) with tumour size at the primary site.
As a result, cetuximab, a monoclonal antibody targeting epidermal growth factor receptor, as well as pembrolizumab and nivolumab, monoclonal antibodies targeting programmed cell death 1 (PD-1), are now US Food and Drug Administration approved for the treatment of R/M HNSCC.
PDCD1 methylation might aid the identification of HNSCC patients potentially benefitting from a radical or alternative treatment, particularly in the context of immunotherapies targeting PD-1/PD-L1.