Differential Expression of PD-L1 during Cell Cycle Progression of Head and Neck Squamous Cell Carcinoma

Schulz, Daniela; Wetzel, Martin; Eichberger, Jonas; Piendl, Gerhard; Brockhoff, Gero; Wege, Anja K.; Reichert, Torsten E.; Ettl, Tobias; Bauer, Richard J.

doi:10.3390/ijms222313087

Open AccessArticle

Differential Expression of PD-L1 during Cell Cycle Progression of Head and Neck Squamous Cell Carcinoma

by

Daniela Schulz

^1,2,

Martin Wetzel

^1,2,

Jonas Eichberger

^1,2,

Gerhard Piendl

³,

Gero Brockhoff

³

,

Anja K. Wege

³

,

Torsten E. Reichert

¹,

Tobias Ettl

¹ and

Richard J. Bauer

^1,2,*

¹

Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, 93053 Regensburg, Germany

²

Department of Oral and Maxillofacial Surgery, Center for Medical Biotechnology, University Hospital Regensburg, 93053 Regensburg, Germany

³

Department of Gynecology and Obstetrics, Medical Center Regensburg, 93053 Regensburg, Germany

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2021, 22(23), 13087; https://doi.org/10.3390/ijms222313087

Submission received: 4 November 2021 / Revised: 26 November 2021 / Accepted: 1 December 2021 / Published: 3 December 2021

(This article belongs to the Special Issue PD-L1, a Master Regulator of Immunity 2.0)

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Abstract

The expression of PD-L1 by tumor cells is mainly associated with its immunosuppressive effect. In fact, PD-1/PD-L1 immune checkpoint inhibitors demonstrated remarkable effects in advanced cancer patients including HNSCC. In this context, irradiation is currently being investigated as a synergistic treatment modality to immunotherapy. However, the majority of HNSCC patients still show little improvement or even hyperprogression. Interestingly, there is increasing evidence for additional cell-intrinsic functions of PD-L1 in tumor cells. In previous studies, we showed that PD-L1 has a strong influence on proliferation, migration, invasion, and survival after irradiation. We demonstrated that cellular expression and localization of PD-L1 differed depending on sensitivity to irradiation. Here, we show that PD-L1 is also differentially expressed during cell cycle progression of HNSCC. Furthermore, cellular localization of PD-L1 also changes depending on a particular cell cycle phase. Moreover, distinct observations occurred depending on the general differentiation status. Overall, the function of PD-L1 cannot be generalized. Rather, it depends on the differentiation status and microenvironment. PD-L1 expression and localization are variable, depending on different factors. These findings may provide insight into why differential response to PD-1/PD-L1 antibody therapy can occur. Detailed understanding of cell-intrinsic PD-L1 functions will further allow antibody-based immunotherapy to be optimized.

Keywords: PD-L1; HNSCC; head and neck; cell cycle inhibition/blockade/progression; palbociclib; aphidicolin; nocodazole; CDK4/CDK6 inhibitor; epithelial/mesenchymal differentiation status

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MDPI and ACS Style

Schulz, D.; Wetzel, M.; Eichberger, J.; Piendl, G.; Brockhoff, G.; Wege, A.K.; Reichert, T.E.; Ettl, T.; Bauer, R.J. Differential Expression of PD-L1 during Cell Cycle Progression of Head and Neck Squamous Cell Carcinoma. Int. J. Mol. Sci. 2021, 22, 13087. https://doi.org/10.3390/ijms222313087

AMA Style

Schulz D, Wetzel M, Eichberger J, Piendl G, Brockhoff G, Wege AK, Reichert TE, Ettl T, Bauer RJ. Differential Expression of PD-L1 during Cell Cycle Progression of Head and Neck Squamous Cell Carcinoma. International Journal of Molecular Sciences. 2021; 22(23):13087. https://doi.org/10.3390/ijms222313087

Chicago/Turabian Style

Schulz, Daniela, Martin Wetzel, Jonas Eichberger, Gerhard Piendl, Gero Brockhoff, Anja K. Wege, Torsten E. Reichert, Tobias Ettl, and Richard J. Bauer. 2021. "Differential Expression of PD-L1 during Cell Cycle Progression of Head and Neck Squamous Cell Carcinoma" International Journal of Molecular Sciences 22, no. 23: 13087. https://doi.org/10.3390/ijms222313087

APA Style

Schulz, D., Wetzel, M., Eichberger, J., Piendl, G., Brockhoff, G., Wege, A. K., Reichert, T. E., Ettl, T., & Bauer, R. J. (2021). Differential Expression of PD-L1 during Cell Cycle Progression of Head and Neck Squamous Cell Carcinoma. International Journal of Molecular Sciences, 22(23), 13087. https://doi.org/10.3390/ijms222313087

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Differential Expression of PD-L1 during Cell Cycle Progression of Head and Neck Squamous Cell Carcinoma

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