Candida albicans induces upregulation of programmed death ligand 1 in oral squamous cell carcinoma. (18th April 2022)

• Record Type: Journal Article
• Authors: Wang, Xu; Zhao, Weiwei; Zhang, Wenqing; Wu, Shuangshuang; Yan, Zhimin
• Is Part Of: Journal of oral pathology & medicine. Volume 51:Number 5(2022)
• Page Start: 444
• Page End: 453
• Publication Date: 2022-04-18
• Subjects: Candida albicans -- oral squamous cell carcinoma -- programmed death ligand 1 -- tumor microenvironment; Dentistry -- Periodicals; Teeth -- Diseases -- Periodicals; 617
• DOI: 10.1111/jop.13298
• Languages: English
• ISSNs: 0904-2512

Abstract

Abstract: Background: 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. Methods: 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. Results: 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. Conclusions: 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.