The Evolving Landscape of PD-1/PD-L1 Pathway in Head and Neck Cancer.

Xin-Wei Qiao,Mei-Chang Huang,Xin-Hua Liang,Jian Jiang,Ya-Jie Tang,Ya-Ling Tang,Xin Pang

doi:10.3389/fimmu.2020.01721

Abstract

Over the past 10 years, cancer immunotherapy has made significant progress in multiple cancer types and has been gradually been applied to clinical cancer care, in which the programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway is one of the most attractive targets. Compared with traditional therapies, the emerging PD-1/PD-L1 blockade immunotherapy exhibited more satisfactory curative effects and lower toxicity for patients with advanced head and neck squamous cell carcinoma (HNSCC). This review analyzes the expression characteristics and clinical significance of PD-1/PD-L1 in HNSCC, the immunosuppressive roles of tumor cell and stromal cell expressing PD-1/PD-L1 in this disease, and presents the development landscape of PD-1/PD-L1 inhibitors, which may provide new curative alternatives for recurrent or metastatic HNSCC.

Highlights

Head and neck cancers (HNC) are the sixth most common malignancies worldwide, with more than 680,000 new cases diagnosed every year [1, 2]
A meta-analysis showed that programmed cell death ligand 1 (PD-L1) positive expression accounted for 42% of 3,105 head and neck squamous cell carcinoma (HNSCC) patients and was associated with human papillomavirus (HPV) status [51]. These results suggest that PD-1/PD-L1 pathway plays a specific role in the pathogenesis and development of HPVpositive HNSCC
PD-1/PD-L1 inhibitors have been widely approved by the Food and Drug Administration (FDA) for a variety of solid tumors and achieved inspiring outcomes

Summary

INTRODUCTION

Head and neck cancers (HNC) are the sixth most common malignancies worldwide, with more than 680,000 new cases diagnosed every year [1, 2]. The over-expression of PD-L1 in tumor cells results from intrinsic and extrinsic regulatory mechanisms, in which IFN-γ secreted by immune cells is the most known potent cytokine inducer [34]. The degree of PD-L1 expression in HNSCC tissues is varied from study to study, which may be for several reasons, such as different protocols for immunohistochemical staining, different antibodies with varying binding affinities, the inconsistent cut-off for positivity, biopsy quality, subjective factors of pathologists’ evaluation and intratumor heterogeneity [45]. These results suggest that PD-1/PD-L1 pathway plays a specific role in the pathogenesis and development of HPVpositive HNSCC

Sample size

Tumor types

NK Cells

Tumor Cells

Findings

CONCLUSION AND PERSPECTIVE