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[Regulation of PD-L1 by MicroRNA in Mismatch Repair Deficient-Colorectal Cancer].
- Source :
-
Gan to kagaku ryoho. Cancer & chemotherapy [Gan To Kagaku Ryoho] 2017 Oct; Vol. 44 (10), pp. 889-891. - Publication Year :
- 2017
-
Abstract
- 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.
Details
- Language :
- Japanese
- ISSN :
- 0385-0684
- Volume :
- 44
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Gan to kagaku ryoho. Cancer & chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 29066686