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Growth and differentiation factor 15 regulates PD-L1 expression in glioblastoma

Authors Peng H, Li Z, Fu J, Zhou R

Received 24 October 2018

Accepted for publication 20 February 2019

Published 2 April 2019 Volume 2019:11 Pages 2653—2661

DOI https://doi.org/10.2147/CMAR.S192095

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 4

Editor who approved publication: Professor Lu-Zhe Sun


Haiqin Peng, Zhanzhan Li, Jun Fu, Rongrong Zhou

Department of Oncology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China

Background: Gliomablastoma multiforme (GBM) is the most fatal form of all brain cancers in human with no successful treatment available. Programmed death-ligand 1 (PD-L1) is a coinhibitory ligand predominantly expressed by tumor cells. Growth differentiation factors (GDFs) are a subfamily of proteins belonging to the transforming growth factor beta superfamily that have functions predominantly in tissue development and cancer.
Purpose: To investigat the expression of GDFs in GBMs, and explored the potential regulatory role of GDFs on PD-L1 expression in GBMs.
Methods: GEO2R program were analyzed for the mRNA expression data of GDFs in GSE4290 dataset. Analysis of TCGA GBM datasets were further determined the relationship between GDFs and PD-L1. Western blot Western blot was used to detect the expression of PD-L1 in GBM cell lines.
Results: GDFs displayed differential patterns of expression with GDF15 and myostatin (MSTN) highly enriched in GBM tissues. We also identified GDF15 as a novel regulator that induces PD-L1 expression in GBM cells. Consistently, GDF15 expression correlated with PD-L1 in TCGA GBM dataset. Further, GDF15 enhanced PD-L1 expression via Smad2/3 pathway in GBM cell line U87, U251 and SHG44, which was inhibited by Smad2/3 inhibitor SIS3. Knockdown of GDF15 attenuated Smad2/3 signaling and reduced PD-L1 expression in A172 and GIC6 glioma cells.
Conclusion: GDF15 might be a novel regulator of PD-L1 expression in GBMs; targeting GDF15/PD-L1 pathway might be a promising therapeutic approach for GBM patients.

Keywords: PD-L1, GDF, GDF15, GBM, immunotherapy

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