Schulz, Daniela and Wetzel, Martin and Eichberger, Jonas and Piendl, Gerhard and Brockhoff, Gero and Wege, Anja K. and Reichert, Torsten E. and Ettl, Tobias and Bauer, Richard 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. ISSN 1422-0067
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | OPEN-LABEL; CANCER; IMMUNOTHERAPY; NIVOLUMAB; RECURRENT; PATHWAY; SIGNALS; PD-L1; HNSCC; head and neck; cell cycle inhibition; blockade; progression; palbociclib; aphidicolin; nocodazole; CDK4; CDK6 inhibitor; epithelial; mesenchymal differentiation status |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Jul 2022 07:02 |
| Last Modified: | 07 Jul 2022 07:02 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45863 |
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