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
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
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DOI：
10.3390/cancers12082045
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发表时间：
2020-08-01
期刊：
影响因子：
5.2
通讯作者：
Kawada, Norifumi
中科院分区：
文献类型：
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作者：
Odagiri, Naoshi;Hai, Hoang;Kawada, Norifumi
免疫检查点抑制剂与抗血管生成剂或局部治疗（例如，经动脉化疗栓塞术（TACE））有望成为不可切除的肝细胞癌（HCC）的护理标准。我们使用基于多重荧光珠的免疫测定法测量了接受乐伐替尼（n= 24）或TACE（n= 22）治疗的HCC患者的16种可溶性检查点蛋白的血浆水平。在乐伐替尼治疗的患者中，第1周sCD 27（可溶性分化抗原集簇27）的血浆水平降低（p= 0.040），sCD 40（p= 0.014）和sTIM-3（p< 0.001）的水平升高，而sCD 27（p< 0.001）的水平在第2周至第4周显著升高。TACE第1周时，除sCD 27外（p= 0.028），sCD 40（p< 0.001），和sTIM-3（可溶性T细胞免疫球蛋白和粘蛋白结构域-3）（p< 0.001），sHVEM水平（可溶性疱疹病毒进入介质）（p= 0.003），sTLR-2（可溶性Toll样受体2）（p= 0.009），sCD80（p= 0.036），sCTLA-4（可溶性细胞毒性T淋巴细胞抗原4）（p= 0.005），sGITR（可溶性糖皮质激素诱导的肿瘤坏死因子受体）（p= 0.030）、sGITRL（可溶性糖皮质激素诱导的TNFR相关配体）（p= 0.090）和sPD-L1（可溶性程序性死亡配体1）（p= 0.070）也增加。在乐伐替尼和TACE治疗组中，可溶性检查点受体及其配体（包括sCTLA-4与sCD 80/sCD 86和sPD-1（可溶性程序性细胞死亡结构域-1）与sPD-L1）的倍数变化呈正相关。我们的研究结果表明，抗血管生成剂和TACE之间的免疫调节作用存在一些有限的差异。来自多中心的进一步研究可能有助于确定有效的联合治疗。
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.