Buparlisib modulates PD-L1 expression in head and neck squamous cell carcinoma cell lines.
Exp Cell Res
; 396(1): 112259, 2020 11 01.
Article
en En
| MEDLINE
| ID: mdl-32898555
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Regulación Neoplásica de la Expresión Génica
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Morfolinas
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Células Epiteliales
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Antígeno B7-H1
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Antineoplásicos Inmunológicos
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Aminopiridinas
Límite:
Humans
Idioma:
En
Revista:
Exp Cell Res
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania