A hemoperfusion column selectively adsorbs LAP+ lymphocytes to improve anti-tumor immunity and survival of tumor-bearing rats.

IF 2.6 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES PLoS ONE Pub Date : 2025-03-07 eCollection Date: 2025-01-01 DOI:10.1371/journal.pone.0305153
Kazuo Teramoto, Yuji Ueda, Ryosuke Murai, Kazumasa Ogasawara, Misako Nakayama, Hirohito Ishigaki, Yasushi Itoh
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Abstract

Reducing the number of immunosuppressive cells in blood is a potential strategy for activating anti-tumor immunity, which provides a promising approach to cancer treatment. In this study, we developed an adsorbent designed to selectively target and adsorb lymphocytes expressing latency-associated peptide (LAP), which is abundantly expressed on the surface of CD4+ regulatory T cells (Tregs) and CD14+ monocytes. We investigated whether diethylenetriamine-conjugated polysulfone adsorbent-based direct hemoperfusion (DHP) enhances anti-tumor immunity in a rat cancer model with KDH-V liver cells. Our findings revealed that DHP significantly reduced LAP+ Tregs in both peripheral blood and tumor tissues in treated mice. Consequently, cytotoxic T-lymphocytes increased in tumor-bearing rats. The anti-tumor effect was negated by the addition of cells detached from the absorbent, indicating that these cells play a crucial role in inhibiting the observed therapeutic effect. The results suggest that depleting LAP+ immunosuppressive cells in blood can enhance anti-tumor immunity and improve survival of patients.

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血液灌流柱选择性吸附LAP+淋巴细胞,提高荷瘤大鼠抗肿瘤免疫能力和生存率。
减少血液中免疫抑制细胞的数量是激活抗肿瘤免疫的一种潜在策略,这为癌症治疗提供了一种有希望的方法。在这项研究中,我们开发了一种吸附剂,旨在选择性靶向和吸附表达潜伏期相关肽(LAP)的淋巴细胞,LAP在CD4+调节性T细胞(Tregs)和CD14+单核细胞表面大量表达。我们研究了二乙烯三胺偶联聚砜吸附剂为基础的直接血液灌流(DHP)是否增强了KDH-V肝细胞大鼠癌症模型的抗肿瘤免疫。我们的研究结果表明,DHP显著降低了治疗小鼠外周血和肿瘤组织中的LAP+ Tregs。因此,荷瘤大鼠的细胞毒性t淋巴细胞增加。加入从吸收剂中分离的细胞后,抗肿瘤作用被否定,这表明这些细胞在抑制观察到的治疗效果中起着至关重要的作用。结果提示,消耗血液中LAP+免疫抑制细胞可增强患者抗肿瘤免疫,提高患者生存率。
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来源期刊
PLoS ONE
PLoS ONE 生物-生物学
CiteScore
6.20
自引率
5.40%
发文量
14242
审稿时长
3.7 months
期刊介绍: PLOS ONE is an international, peer-reviewed, open-access, online publication. PLOS ONE welcomes reports on primary research from any scientific discipline. It provides: * Open-access—freely accessible online, authors retain copyright * Fast publication times * Peer review by expert, practicing researchers * Post-publication tools to indicate quality and impact * Community-based dialogue on articles * Worldwide media coverage
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