Abstract
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.
Highlights
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
Univariate Cox regression analysis identified that hemoglobin
We identified significant changes for commonly studied inhibitory factors such as soluble programmed cell death protein 1 (sPD-1), soluble programmed cell death-ligand 1 (sPD-L1) or sCTLA-423–26, and for less well-studied checkpoint proteins
Summary
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. Sorafenib treatment in patients with advanced HCC revealed dynamic changes of soluble checkpoint protein levels. We measured the concentrations of 16 soluble immune checkpoint proteins, using multiplexed fluorescent bead-based immunoassays, in plasma samples obtained from patients with advanced HCC. We studied changes in the plasma levels of soluble proteins during the early stages of sorafenib treatment
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