MYC inhibition increases PD-L1 expression induced by IFN-γ in hepatocellular carcinoma cells

Publication date: September 2018

Source: Molecular Immunology, Volume 101

Author(s): Jiahuan Zou, Mengwei Zhuang, Xiaopeng Yu, Na Li, Rudi Mao, Zhida Wang, Jianing Wang, Xiaoyan Wang, Huaiyu Zhou, Lining Zhang, Yongyu Shi

Abstract

The effectiveness of immunotherapy targeting the immune checkpoint PD-L1/PD-1 pathway highlights importance of elucidating the regulatory mechanisms of PD-L1 expression in cancer cells. Previous studies demonstrate that oncogene MYC up-regulates PD-L1 expression in lymphomas. In the present study, we investigated the regulatory role of MYC in the PD-L1 expression induced by IFN-γ in HCC cells. Unexpectedly, knockdown of MYC expression using siRNA assay increased the inducible expression of PD-L1 both at mRNA and protein levels. Mechanistically, the inhibition of MYC elevated expression of STAT1, a critical component of IFN-γ signaling pathway, leading to the elevation of PD-L1 expression in HCC cells exposed to IFN-γ. These results suggest that MYC may down-regulate PD-L1 expression in the context of HCC. This study implicates that a combination therapy targeting MYC function and PD-L1/PD-1 pathway might be effective for treatment of HCC.

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