PD-L1 expression fluctuates during the cell cycle in human cancer

Background A cross-talk between certain oncogenic signaling pathways and PD-L1 expression is emerging. Oncogenic signals often promote cell proliferation, an aggressive cancer hallmark, thus we hypothesized that tumor proliferation rates can influence the levels of PD-L1. Methods We used U251MG and SF767MG glioma cell lines that constitutively express PD-L1 and analyzed the expression level of PD-L1 in condition of serum deprivation and during the phases of cell culture growth. Also, we investigated whether tumor proliferative rates influenced the subcellular distribution of FKBP51s cochaperone, that regulates PD-L1 expression at translational level. Result Our findings suggested that PD-L1 upregulation was associated with DNA synthesis. FKBP51s was detected in ER during DNA replication, but in the nucleus during cell division. A chromatin immunoprecipitation assay using A375-FKBP51 KO melanoma cell line showed that both FKBP51 isoforms can bind the promoter of cyclin D. However, an open chromatin status was found in FKBP51, but FKBP51s enriched chromatin. Conclusion Our study suggests that cell proliferation is an additional factor that drives PD-L1 expression and uncovers an unknown role for its cochaperone that, after assisting PD-L1 production, becomes nuclear in concomitance with the decline of DNA replication and PD-L1 expression