Fiedler, Mathias and Schulz, Daniela and Piendl, Gerhard and Brockhoff, Gero and Eichberger, Jonas and Menevse, Ayse-Nur and Beckhove, Philipp and Hautmann, Matthias and Reichert, Torsten E. and Ettl, Tobias and Bauer, Richard J. (2020) Buparlisib modulates PD-L1 expression in head and neck squamous cell carcinoma cell lines. EXPERIMENTAL CELL RESEARCH, 396 (1): 112259. ISSN 0014-4827, 1090-2422
Full text not available from this repository. (Request a copy)Abstract
High expression of the immune checkpoint receptor PD-L1 is associated with worse patient outcome in a variety of human cancers, including head and neck squamous cell carcinoma (HNSCC). Binding of PD-L1 with its partner PD-1 generates an inhibitory signal that dampens the immune system. Immunotherapy, that is blocking the PD-1/PD-L1 checkpoint, has proven to be an effective tool in cancer therapy. However, not all patients are able to benefit from this immune checkpoint inhibition. Therefore, evidence is growing of intrinsic PD-L1 signaling in cancer cells. For example, intrinsic PD-L1 expression was associated with PI3K/Akt/mTOR signaling, which is part of diverse oncogenic processes including cell proliferation, growth and survival. In this study we demonstrate the effects of PI3K/Akt/mTOR pathway inhibition by buparlisib on PD-L1 expression in HNSCC cell lines. After buparlisib treatment for 72 h, PD-L1 was downregulated in total cell lysates of HNSCC cells. Moreover, flow cytometry revealed a downregulation of PD-L1 membrane expression. Interestingly, the buparlisib mediated effects on PD-L1 expression were reduced by additional irradiation. In PD-L1 overexpressing cells, the buparlisib induced inhibition of proliferation was neutralized. In summary, our findings imply that blocking the PI3K/Akt/mTOR pathway could be a good additional therapy for patients who show poor response to immune checkpoint therapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | WILD-TYPE; CANCER; ANTITUMOR; IMMUNORESISTANCE; PATHWAY; SIGNALS; MODELS; Head and neck squamous cell carcinoma; PI3-Kinase; Akt/PKB; Immune checkpoint; PD-L1; Buparlisib |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie Medicine > Lehrstuhl für Strahlentherapie Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Mar 2021 11:00 |
| Last Modified: | 08 Mar 2021 11:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43479 |
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