PD-L1: a novel prognostic biomarker in head and neck squamous cell carcinoma

Abstract

BackgroundThe PD-1 receptor and its ligands PD-L1 and PD-L2 are known to be significantly involved in T-cell regulation. Recent studies suggest that PD-L1 expression in malignant tumors contributes to an immunosuppressive microenvironment and disruption of antitumoral immune response. Drugs targeting this pathway are already tested in clinical trials against several tumor entities with promising results. However, until now comprehensive data with regard to PD-L1 and PD-L2 expression in head and neck squamous cell carcinoma (HNSCC) is still lacking.Patients and methodsWe assessed PD-L1 and PD-L2 expression via immunohistochemistry in two independent cohorts of 293 HNSCC patients.ResultsA significant subset of HNSCC showed high expression levels of PD-L1. Most remarkable, we detected a strong correlation between PD-L1 expression and overall survival time in both HNSCC cohorts. Further, in multivariate cox proportional hazard models, PD-L1 dominates as the strongest prognostic factor of patient's outcome in HNSCC, leaving even tumor stage and distant metastasis behind. Moreover, strong PD-L1 expression was associated with the presence of distant metastases in a subset of cases.ConclusionsIn summary, while the significance of PD-L2 in HNSCC seems to minor, we show that PD-L1 expression is common in HNSCC and, more importantly, a both robust and strong prognostic biomarker. In this respect, our results provide hints on further application of therapies targeting the PD-1/PD-L1 pathway in HNSCC. Investigation of response and outcome of patients receiving anti-PD-1/PD-L1 containing therapies in correlation with PD-L1 expression analysis should be an important task for the future.STATEMENT OF TRANSLATIONAL RELEVANCEIn spite of improved treatment options and increasing knowledge of molecular alterations in HNSCC, the survival rate has not been dramatically changed in the past decades. Pies are missing in HNSCC. One promising candidate in cancer immune therapy is PD-L1.Drugs targeting PD-L1 or its receptor PD-1 are subject of several clinical studies in different cancer entities. However, comprehensive data about PD-L1 expression in HNSCC and therefore a rational basis for anti PD-L1/PD-1 therapy in HNSCC is lacking. Here, we provide wide-ranging data about PD-L1 expression in HNSCC of all major localizations. We observed a strong correlation between expression of PD-L1 and reduced overall survival time. Furthermore, high PD-L1 expression was identified as a strong prognostic factor of patient's outcome when verified together with recognized prognostic factors.

The immune microenvironment and expression of PD‐L1, PD‐1, PRAME and MHC I in salivary duct carcinoma

“…PD‐L1 expression in TCs impairs T‐cell regulation, disrupts the antitumoral immune response, and contributes to an immunosuppressive microenvironment, allowing tumour immune escape . In several cancer types, such as HNSCC, oropharyngeal squamous cell carcinoma (SCC), pulmonary adenocarcinoma, oesophageal SCC, and urothelial carcinoma, PD‐L1 immunoexpression has been reported to be associated with advanced tumour stage, poor clinical outcome, and/or decreased overall survival. Similarly, in a cohort of 219 salivary gland carcinomas of various types, including 31 SDCs, Mukaigawa et al .…”

“…The normal physiological interaction between PD‐L1 and PD‐1 inhibits the immune response and promotes self‐tolerance . In many human cancers, including head and neck carcinoma, the PD‐1/PD‐L1 pathway is used by TCs to evade recognition by the host immune system …”

Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy

“…PD-1 and PD-L1 expression currently remain the most significant tissue biomarkers. PD-L1 expression has been associated with postchemotherapy (docetaxel/platinum/5-fluorouracil regimen) status, 127 co-occurrence with p16 INK4 expression, 131 and poorer OS 124,126,128 (but improved RFS 125,129 and OS 125,130 ). Among these studies, associations between high PD-L1 expression and favorable OS were all demonstrated in post-surgery HNSCC patients.…”

Squamous Cell Carcinoma Antigen-encoding Genes SERPINB3/B4 as Potentially Useful Markers for the Stratification of HNSCC Tumours

“…Because of the cost of these treatments and their toxicity, identifying biological parameters that predict their efficacy in individual patients is required (26,34). Out of the five most important parameters that define the «tumour immunogram» (26), we found that at least three are associated with the SERPINB3 status: i) the presence of an immune infiltrate; ii) high expression of the immune checkpoint modulator PD-L1, a marker associated with a better response to immunotherapy in HNSCC (7,8,35); iii) tumour sensitivity to immune effectors, such as Ifn-γ, as shown here with the IFNG signature reported by Chow et al (27). Interestingly, similarly to our observations with SERPINB3, high expression levels of another tumour marker, Alpha-foetoprotein (AFP), were recently found in hepatocellular carcinoma cells with increased expression of PD-L1 (36).…”