Candida albicans induces upregulation of programmed death ligand 1 in oral squamous cell carcinoma

The potential association between Candida albicans (C. albicans) infection and oral squamous cell carcinoma (OSCC) has been noticed for a long time. Programmed death ligand-1 (PD-L1) is a key molecule of tumor immune escape and tumor progression. This study aimed to explore whether C. albicans could influence PD-L1 expression in OSCC in vitro and in mouse model.OSCC cell lines (Cal27 and HN6) were infected with C. albicans for 2 and 24 h, then PD-L1 expression was detected by quantitative real-time polymerase chain reaction (RT-qPCR), western blot (WB), and flow cytometry (FCM). To identify the underlying mechanisms, PD-L1 expression in OSCC cells treated with heat-inactivated C. albicans or with biofilm metabolites derived from C. albicans were explored respectively. Meanwhile, signaling pathways involved in PD-L1 regulation were explored by RT-qPCR, and the candidate genes were verified by WB. Moreover, an OSCC mouse model induced by 4-nitroquinoline-1 oxide was used to further explore the role of C. albicans infection in PD-L1 expression in vivo.C. albicans and heat-inactivated C. albicans upregulated the PD-L1 expression in Cal27 and HN6 cells. Various signaling pathways involved in PD-L1 regulation were influenced by C. albicans infection. Among them, TLR2/MyD88 and TLR2/NF-κB pathways might participate in this process. Furthermore, PD-L1 expression in oral mucosa epithelium was upregulated by C. albicans infection in both normal and OSCC mice.This study suggests that C. albicans could induce upregulation of PD-L1 in OSCC in vitro and in mouse model, which might due to the activation of TLR2/MyD88 and TLR2/NF-κB pathways.