Regulation of PD-L1 by MicroRNA in Mismatch Repair Deficient-Colorectal Cancer
Ashizawa, M.; Okayama, H.; Aung Kyi Thar Min; Noda, M.; Aoto, K.; Nakajima, T.; Ishigame, T.; Mimura, K.; Kono, K.
Gan to Kagaku Ryoho. Cancer and ChemoTherapy 44(10): 889-891
2017
ISSN/ISBN: 0385-0684 PMID: 29066686 Document Number: 692469
Programmed cell death 1(PD-1)/PD-ligand 1(PD-L1)immune checkpoint blockade has emerged as a promising therapeutic strategy in various types of cancer. In a recent phase II clinical trial, treatment with the anti-PD-1 agent, pembrolizumab, resulted in considerable clinical benefit in patients with mismatch repair(MMR)-deficient colorectal cancer(CRC). Upregulation of PD-1on T-cells and PD-L1 on tumor cells induces inhibitory signals to suppress T-cell activation, leading to an immune-suppressive microenvironment particularly in MMR-deficient tumors. However, the regulation of PD-L1 expression on CRC cells is poorly understood. We hypothesized that certain microRNAs(miRNAs)are involved in the immunosuppressive microenvironment by directly targeting PD-L1. We identified candidate miRNAs by RNA-sequence analyses for mRNA and miRNA expression obtained from the TCGA colon adenocarcinoma database combined with miRNA target prediction programs. We found that forced miRNA expression could decrease PD-L1 expression on cancer cell lines. Our findings may facilitate an understanding of the role of miRNAs in PD-L1 regulation and also suggest potential miRNAs to serve as biomarkers and therapeutic targets for cancer immunotherapy.