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.

免疫检查点受体PD-L1的高表达与包括头颈部鳞状细胞癌（HNSCC）在内的多种人类癌症的患者预后差有关。PD-L1及其伴侣PD-1的结合会产生抑制信号，从而抑制免疫系统。免疫疗法阻碍了PD-1 / PD-L1检查点，已被证明是癌症治疗的有效工具。但是，并非所有患者都能从这种免疫检查点抑制中受益。因此，越来越多的证据表明癌细胞中固有的PD-L1信号传导。例如，固有的PD-L1表达与PI3K / Akt / mTOR信号传导相关，这是包括细胞增殖，生长和存活在内的多种致癌过程的一部分。在这项研究中，我们证明了buparlisib对PI3K / Akt / mTOR通路的抑制作用对HNSCC细胞系中PD-L1表达的影响。buparlisib治疗72小时后，PD-L1在HNSCC细胞的总细胞裂解物中下调。此外，流式细胞仪显示PD-L1膜表达下调。有趣的是，通过额外的照射减少了buparlisib对PD-L1表达的介导作用。在PD-L1过表达的细胞中，buparlisib诱导的增殖抑制被中和。总而言之，我们的发现表明，对于免疫检查点治疗反应较差的患者，阻断PI3K / Akt / mTOR途径可能是一种很好的辅助治疗方法。流式细胞仪显示PD-L1膜表达下调。有趣的是，通过额外的照射减少了buparlisib对PD-L1表达的介导作用。在PD-L1过表达的细胞中，buparlisib诱导的增殖抑制被中和。总而言之，我们的发现表明，对于免疫检查点治疗反应较差的患者，阻断PI3K / Akt / mTOR途径可能是一种很好的辅助治疗方法。流式细胞仪显示PD-L1膜表达下调。有趣的是，通过额外的照射减少了buparlisib对PD-L1表达的介导作用。在PD-L1过表达的细胞中，buparlisib诱导的增殖抑制被中和。总而言之，我们的发现表明，对于免疫检查点治疗反应较差的患者，阻断PI3K / Akt / mTOR途径可能是一种很好的辅助治疗方法。