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Article

Early Change in the Plasma Levels of Circulating Soluble Immune Checkpoint Proteins in Patients with Unresectable Hepatocellular Carcinoma Treated by Lenvatinib or Transcatheter Arterial Chemoembolization

Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan
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Author to whom correspondence should be addressed.
Cancers 2020, 12(8), 2045; https://doi.org/10.3390/cancers12082045
Received: 25 June 2020 / Revised: 12 July 2020 / Accepted: 21 July 2020 / Published: 24 July 2020
(This article belongs to the Special Issue Immunotherapy in Hepatocellular Carcinoma)
Immune checkpoint inhibitors, combined with anti-angiogenic agents or locoregional treatments (e.g., transarterial chemoembolization (TACE)), are expected to become standard-of-care for unresectable hepatocellular carcinoma (HCC). We measured the plasma levels of 16 soluble checkpoint proteins using multiplexed fluorescent bead-based immunoassays in patients with HCC who underwent lenvatinib (n = 24) or TACE (n = 22) treatment. In lenvatinib-treated patients, plasma levels of sCD27 (soluble cluster of differentiation 27) decreased (p = 0.040) and levels of sCD40 (p = 0.014) and sTIM-3 (p < 0.001) were increased at Week 1, while levels of sCD27 (p < 0.001) were increased significantly at Weeks 2 through 4. At Week 1 of TACE, in addition to sCD27 (p = 0.028), sCD40 (p < 0.001), and sTIM-3 (soluble T-cell immunoglobulin and mucin domain–3) (p < 0.001), levels of sHVEM (soluble herpesvirus entry mediator) (p = 0.003), sTLR-2 (soluble Toll-like receptor 2) (p = 0.009), sCD80 (p = 0.036), sCTLA-4 (soluble cytotoxic T-lymphocyte antigen 4) (p = 0.005), sGITR (soluble glucocorticoid-induced tumor necrosis factor receptor) (p = 0.030), sGITRL (soluble glucocorticoid-induced TNFR-related ligand) (p = 0.090), and sPD-L1 (soluble programmed death-ligand 1) (p = 0.070) also increased. The fold-changes in soluble checkpoint receptors and their ligands, including sCTLA-4 with sCD80/sCD86 and sPD-1 (soluble programmed cell death domain–1) with sPD-L1 were positively correlated in both the lenvatinib and TACE treatment groups. Our results suggest that there are some limited differences in immunomodulatory effects between anti-angiogenic agents and TACE. Further studies from multicenters may help to identify an effective combination therapy. View Full-Text
Keywords: HCC; liver cancer; molecular-targeted agent; TACE; tyrosine kinase inhibitor HCC; liver cancer; molecular-targeted agent; TACE; tyrosine kinase inhibitor
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MDPI and ACS Style

Odagiri, N.; Hai, H.; Thuy, L.T.T.; Dong, M.P.; Suoh, M.; Kotani, K.; Hagihara, A.; Uchida-Kobayashi, S.; Tamori, A.; Enomoto, M.; Kawada, N. Early Change in the Plasma Levels of Circulating Soluble Immune Checkpoint Proteins in Patients with Unresectable Hepatocellular Carcinoma Treated by Lenvatinib or Transcatheter Arterial Chemoembolization. Cancers 2020, 12, 2045. https://doi.org/10.3390/cancers12082045

AMA Style

Odagiri N, Hai H, Thuy LTT, Dong MP, Suoh M, Kotani K, Hagihara A, Uchida-Kobayashi S, Tamori A, Enomoto M, Kawada N. Early Change in the Plasma Levels of Circulating Soluble Immune Checkpoint Proteins in Patients with Unresectable Hepatocellular Carcinoma Treated by Lenvatinib or Transcatheter Arterial Chemoembolization. Cancers. 2020; 12(8):2045. https://doi.org/10.3390/cancers12082045

Chicago/Turabian Style

Odagiri, Naoshi, Hoang Hai, Le T.T. Thuy, Minh P. Dong, Maito Suoh, Kohei Kotani, Atsushi Hagihara, Sawako Uchida-Kobayashi, Akihiro Tamori, Masaru Enomoto, and Norifumi Kawada. 2020. "Early Change in the Plasma Levels of Circulating Soluble Immune Checkpoint Proteins in Patients with Unresectable Hepatocellular Carcinoma Treated by Lenvatinib or Transcatheter Arterial Chemoembolization" Cancers 12, no. 8: 2045. https://doi.org/10.3390/cancers12082045

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