Buparlisib modulates PD-L1 expression in head and neck squamous cell carcinoma cell lines.

Buparlisib modulates PD-L1 expression in head and neck squamous cell carcinoma cell lines.:

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Buparlisib modulates PD-L1 expression in head and neck squamous cell carcinoma cell lines.

Exp Cell Res. 2020 Sep 05;:112259

Authors: Fiedler M, Schulz D, Piendl G, Brockhoff G, Eichberger J, Menevse AN, Beckhove P, Hautmann M, Reichert TE, Ettl T, Bauer RJ

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 overexpressed 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.



PMID: 32898555 [PubMed - as supplied by publisher]