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Clinical significance of circulating soluble immune checkpoint proteins in sorafenib-treated patients with advanced hepatocellular carcinoma

In 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 sorafe...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042216/
https://www.ncbi.nlm.nih.gov/pubmed/32099055
http://dx.doi.org/10.1038/s41598-020-60440-5
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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
author_facet 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
author_sort Dong, Minh Phuong
collection PubMed
description In 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.
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spelling pubmed-70422162020-03-03 Clinical significance of circulating soluble immune checkpoint proteins in sorafenib-treated patients with advanced hepatocellular carcinoma 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 Sci Rep Article In 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. Nature Publishing Group UK 2020-02-25 /pmc/articles/PMC7042216/ /pubmed/32099055 http://dx.doi.org/10.1038/s41598-020-60440-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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
Clinical significance of circulating soluble immune checkpoint proteins in sorafenib-treated patients with advanced hepatocellular carcinoma
title Clinical significance of circulating soluble immune checkpoint proteins in sorafenib-treated patients with advanced hepatocellular carcinoma
title_full Clinical significance of circulating soluble immune checkpoint proteins in sorafenib-treated patients with advanced hepatocellular carcinoma
title_fullStr Clinical significance of circulating soluble immune checkpoint proteins in sorafenib-treated patients with advanced hepatocellular carcinoma
title_full_unstemmed Clinical significance of circulating soluble immune checkpoint proteins in sorafenib-treated patients with advanced hepatocellular carcinoma
title_short Clinical significance of circulating soluble immune checkpoint proteins in sorafenib-treated patients with advanced hepatocellular carcinoma
title_sort clinical significance of circulating soluble immune checkpoint proteins in sorafenib-treated patients with advanced hepatocellular carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042216/
https://www.ncbi.nlm.nih.gov/pubmed/32099055
http://dx.doi.org/10.1038/s41598-020-60440-5
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