Chronic exposure to arsenic promotes lung cancer. Human studies have identified immunosuppression as a risk factor for cancer development. The immune checkpoint pathway of Programmed cell death 1 ligand (PD-L1) and its receptor (programmed cell death receptor 1, PD-1) is the most studied mechanism of immunosuppression. We have previously shown that prolonged arsenic exposure induced cell transformation of BEAS-2B cells, a human lung epithelial cell line. More recently our study further showed that arsenic induced PD-L1 up-regulation, inhibited T cell effector function, and enhanced lung tumor formation in the mice. In the current study, using arsenic-induced BEAS-2B transformation as a model system we investigated the mechanism underlying PD-L1 up-regulation by arsenic. Our data suggests that Lnc-DC, a long non-coding RNA, and signal transducer and activator of transcription 3 (STAT3) mediates PD-L1 up-regulation by arsenic. • PD-L1 is up-regulated on arsenic-transformed BEAS-2B cells. • STAT3 is activated in the transformed cells and knockdown of STAT3 reverses arsenic-induced PD-L1 up-regulation. • Lnc-DC acts as an up-stream regulator of arsenic-induced STAT3 activation. • Lnc-DC/STAT3 cascade mediates PD-L1 up-regulation during arsenic-induced transformation of BEAS-2B cells. [ABSTRACT FROM AUTHOR]