Author:
Dong Minh Phuong,Enomoto Masaru,Thuy Le Thi Thanh,Hai Hoang,Hieu Vu Ngoc,Hoang Dinh Viet,Iida-Ueno Ayako,Odagiri Naoshi,Amano-Teranishi Yuga,Hagihara Atsushi,Fujii Hideki,Uchida-Kobayashi Sawako,Tamori Akihiro,Kawada Norifumi
Abstract
AbstractIn hepatocellular carcinoma (HCC), the clinical significance of soluble immune checkpoint protein levels as predictors of patient outcomes or therapeutic responses has yet to be defined. This study profiled the baseline levels of sixteen soluble checkpoint proteins and their changes following sorafenib treatment for HCC. Plasma samples were obtained from 53 patients with advanced HCC at baseline, week 1, 2 and 4 of sorafenib treatment and tested the concentrations of 16 soluble checkpoint proteins using multiplexed fluorescent bead-based immunoassays. Multivariate analysis showed high sBTLA levels at baseline were an independent predictor of poor overall survival (p = 0.038). BTLA was highly expressed in T cells and macrophages in peritumoral areas. At week 2, sCD27 levels were decreased compared to baseline. By contrast, the concentrations of most inhibitory proteins, including sBTLA, sLAG-3, sCTLA-4, sPD-1, sCD80, sCD86 and sPD-L1, had significantly increased. The fold-changes of soluble checkpoint receptors and their ligands, including sCTLA-4 with sCD80/sCD86, sPD-1 with sPD-L1; and the fold-changes of sCTLA-4 with sBTLA or sPD-1 were positively correlated. sBTLA may be a good biomarker for predicting overall survival in HCC patients. Sorafenib treatment in patients with advanced HCC revealed dynamic changes of soluble checkpoint protein levels.
Funder
Ministry of Health, Labour and Welfare
Japan Society for the Promotion of Science
Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science
Publisher
Springer Science and Business Media LLC
Cited by
44 articles.
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