Journal
MOLECULAR IMMUNOLOGY
Volume 101, Issue -, Pages 203-209Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2018.07.006
Keywords
PD-L1; B7-H1; CD274; MYC; Immune checkpoints; Hepatocelluar carcinomas
Categories
Funding
- National Nature Science Foundation of China [81372264, 81672806]
- Key Research and Development Program of Shandong Province [2017GSF218066]
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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-gamma 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-gamma signaling pathway, leading to the elevation of PD-L1 expression in HCC cells exposed to IFN-gamma. 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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