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Increased PD-L1 expression in radioresistant HNSCC cell lines after irradiation affects cell proliferation due to inactivation of GSK-3beta


The cover for issue 5 of Oncotarget features Figure 5, "PD-L1 function in RR cell lines," by Schulz, et al.

RR cells showed prolonged survival as well as delayed and diminished apoptosis after irradiation with vimentin expression but no E-cadherin expression, whereas RS cell lines died early and exhibited early apoptosis after irradiation and high vimentin expression.

Moreover, the research team observed a radiation dose dependent increase of total PD-L1 protein expression in RR cell lines up to 96h after irradiation compared to non-irradiated cells.

Co-immunoprecipitation experiments revealed decreased interaction of GSK-3beta with PD-L1 in non-IRR compared to irradiated RR cells leading to PD-L1 stabilization in RR cells.

Figure 5: PD-L1 function in RR cell lines. (A) WST-1 viability assay after siRNA knockdown of PD-L1 in RR HNSCC cell lines. All cell lines with PD-L1 knockdown showed a substantial decrease of proliferation compared to cells transfected with scrambled siRNA (NT) as control during the course of 96h. (B) The average doubling time of PD-L1 knockdown cells was 115,9h compared to NT control cells with 46,8h. NT= non-targeting, scrambled non-specific siRNA. Two-way ANOVA * = p < 0,05, ** = p < 0,01, *** = p < 0,001.

Prof Dr. Tobias Ettl from the Department of Oral and Maxillofacial Surgery, University Hospital Regensburg in Germany and the Center for Medical Biotechnology, said "With more than 600.000 new diagnosis each year head and neck squamous cell carcinoma is the 6th most common form of cancer worldwide with a strongly increasing incidence over the last 10 years.Recent studies show that PD-L1 expressing cancer cells have the ability to evade immune response. Multidisciplinary approach of irradiation combined with a blockade of the PD-1/PD-L1 axis showed remarkable clinical outcomes for various tumor entities and in patients with poor prognosis. However, a considerable part of HNSCC patients still shows little improvement or even hyperprogression."

PD-L1 expression is common in many solid human cancers including colorectal cancer, gastric cancer, esophageal cancer, hepatocellular carcinoma, melanoma, glioblastoma, lung cancer, and oral squamous cell carcinoma .

Together with PD Dr. Richard Bauer and Daniela Schulz from the Center for Medical Biotechnolgy in Regensburg, they investigate the tumor cell intrinsic function of PD-L1 which they suggest to be dependent on the basic molecular setup of tumor cells. This setup determines raidoresistancy or radiosensitivity and principally the expression, localization, interaction and function of proteins such as PD-L1. Therefore,in this study the team examined PD-L1 expression and cell intrinsic function in radioresistant and radiosensitive HNSCC cell lines before and after irradiation.

The Bauer research team concluded, "Our data suggest a longer turnover time of PD-L1 in IRR RR cells due to GSK-3beta inactivation and subsequent PD-L1 stabilization."

Full text - https://doi.org/10.18632/oncotarget.26542

Correspondence to - Richard Josef Bauer - richard.bauer@ukr.de

Keywords - PD-L1, immune checkpoint, head and neck cancer, irradiation, GSK-3beta

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