Using PD-L1 to Induce Chemosensitization of Head and Neck Squamous Cell Carcinoma

Abstract

Objectives:

(1) Investigate the impact of programmed cell death ligand 1 (PD-L1) on the response to Cisplatin (CDDP) therapy in head and neck squamous cell carcinoma (HNSCC). (2) Quantify the effect of CDDP treatment on the expression of PD-L1 in HNSCC cells. (3) Evaluate the impact of PD-L1 down-regulation on the chemosensitivty of HNSCC cells. (4) Describe the implications of PD-L1 modulation on the efficacy of current platinum-based chemotherapeutic agents in HNSCC.

Methods:

In vitro experiments were performed from November 2013 to January 2014 at the University of Pennsylvania Gene and Molecular Therapy Laboratory with 4 well-characterized human HNSCC cell lines. Quantitative polymerase chain reaction (qPCR) and western blot were conducted to determine the baseline and post-CDDP treatment PD-L1 gene expression. Knockdown of PD-L1 expression using siRNA was then performed to induce chemosensitization of HNSCC cells to CDDP. Cells treated with CDDP were compared with untreated controls to evaluate cytotoxicity.

Results:

Treatment of HNSCC cells with CDDP resulted in increased transcription and translation of PD-L1 compared with baseline levels. Subsequent knockdown of PD-L1 expression in HNSCC cells using siRNA resulted in increased CDDP cytotoxicity compared with control HNSCC cells.

Conclusions:

Increased PD-L1 expression in response to CDDP therapy and improved chemosensitization with its down-regulation are significant findings that highlight the role of PD-L1 in determining the efficacy of chemotherapeutic agents. Our findings demonstrate that disruption of the PD-L1 protein leads to increased sensitivity of HNSCC cells to CDDP, suggesting a potential combination therapeutic strategy for patients with CDDP-resistant HNSCC.