Potential Roles of Serum Exosomal CD155 and its Impact on NK Cell Immunosuppression in Hepatocellular Carcinoma.

IF 1.9 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Balkan Medical Journal Pub Date : 2025-05-05 DOI:10.4274/balkanmedj.galenos.2025.2025-1-129

Wenzheng Han, Jinrong Lv, Mintuo Wang, Xiaoxin Wu, Dongdong Sun, Wenwen Chen, Yingying Wang, Wenjie Zhou, Yuxuan Yang, Jia Bao, Qingzhen Han, Xiaopeng Chen, Fei Guo, Gang Feng, Min Li, Qing Chen

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引用次数: 0

Abstract

Background: Targeted therapies directed at tumor immune checkpoint, like programmed death-ligand (PD-L)1/programmed death (PD)-1, have shown remarkable progress. Nevertheless, treatment efficacy in hepatocellular carcinoma (HCC) is notably compromised due to the intricate immune microenvironment. Exploring alternative checkpoints beyond PD-L1/PD-1, including those not located on the cell surface, may improve our understanding of their roles in areas like diagnostic potential and immune tolerance in HCC.

Aims: To explore the roles of serum exosomal CD155 (exo-CD155) in HCC.

Study design: Experimental study.

Methods: We separated and analyzed serum exosomes from HCC patients. We quantified the concentrations of serum soluble CD155 (sCD155) and serum exo-CD155, and examined their association with disease progression, hepatitis B surface antigen (HBsAg) presence, and the concentrations of α-fetoprotein fraction L3 (AFP-L3) or alpha-fetoprotein (AFP). Additionally, we assessed the diagnostic effect through the receiver operating characteristic (ROC) curve, and the immune suppressive effect on natural killer (NK) cells of exo-CD155.

Results: This study reveal elevated exo-CD155 levels in all HCC patients, with a significant increase in early-stage patients, exhibiting normal AFP/AFP-L3 or HBsAg-positive status. Exo-CD155 is linked to the progression of HCC and shows significant diagnostic effectiveness for the disease. Furthermore, the incubation of NK-92MI with exosomes derived from HCC patients leads to a substantial reduction in immune function, which can be partially counteracted with an antibody that blocks T cell immune receptor immunoglobulin and ITIM domains, (TIGIT)-blocking antibody.

Conclusion: These results disclose exo-CD155 shows promise for serving as a biomarker for HCC, especially in early-stage patients or those with normal AFP/AFP-L3 levels. Moreover, serum exosomes from HCC patients suppress NK cell immune functions through the TIGIT/CD155 pathway, contributing to immune tolerance in HCC.

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肝细胞癌中血清外泌体CD155的潜在作用及其对NK细胞免疫抑制的影响

背景：针对肿瘤免疫检查点的靶向治疗，如程序性死亡配体（PD- l）1/程序性死亡(PD)-1，已取得显著进展。然而，由于复杂的免疫微环境，肝细胞癌（HCC）的治疗效果明显受到损害。探索PD-L1/PD-1以外的其他检查点，包括那些不位于细胞表面的检查点，可能会提高我们对它们在HCC诊断潜力和免疫耐受等领域的作用的理解。目的：探讨血清外泌体CD155 （exo-CD155）在HCC中的作用。研究设计：实验研究。方法：对HCC患者血清外泌体进行分离分析。我们量化了血清可溶性CD155 （sCD155）和血清外显子CD155的浓度，并检测了它们与疾病进展、乙型肝炎表面抗原（HBsAg）存在以及α-胎蛋白部分L3 （AFP-L3）或甲胎蛋白（AFP）浓度的关系。此外，我们通过受试者工作特征（ROC）曲线评估诊断效果，以及对exo-CD155自然杀伤（NK）细胞的免疫抑制作用。结果：本研究显示所有HCC患者中exo-CD155水平升高，早期患者显著升高，表现为正常的AFP/AFP- l3或hbsag阳性状态。Exo-CD155与HCC的进展有关，并显示出对该疾病的显著诊断有效性。此外，NK-92MI与来自HCC患者的外泌体孵育会导致免疫功能的显著降低，这可以通过阻断T细胞免疫受体免疫球蛋白和ITIM结构域的抗体（TIGIT）阻断抗体部分抵消。结论：这些结果表明，exo-CD155有望作为HCC的生物标志物，特别是在早期患者或AFP/AFP- l3水平正常的患者中。此外，HCC患者的血清外泌体通过TIGIT/CD155途径抑制NK细胞免疫功能，有助于HCC的免疫耐受。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Balkan Medical Journal MEDICINE, GENERAL & INTERNAL-

CiteScore

4.10

自引率

6.70%

发文量

审稿时长

6-12 weeks

期刊介绍： The Balkan Medical Journal (Balkan Med J) is a peer-reviewed open-access international journal that publishes interesting clinical and experimental research conducted in all fields of medicine, interesting case reports and clinical images, invited reviews, editorials, letters, comments and letters to the Editor including reports on publication and research ethics. The journal is the official scientific publication of the Trakya University Faculty of Medicine, Edirne, Turkey and is printed six times a year, in January, March, May, July, September and November. The language of the journal is English. The journal is based on independent and unbiased double-blinded peer-reviewed principles. Only unpublished papers that are not under review for publication elsewhere can be submitted. Balkan Medical Journal does not accept multiple submission and duplicate submission even though the previous one was published in a different language. The authors are responsible for the scientific content of the material to be published. The Balkan Medical Journal reserves the right to request any research materials on which the paper is based. The Balkan Medical Journal encourages and enables academicians, researchers, specialists and primary care physicians of Balkan countries to publish their valuable research in all branches of medicine. The primary aim of the journal is to publish original articles with high scientific and ethical quality and serve as a good example of medical publications in the Balkans as well as in the World.