P-选择素已被证明可以通过促进调节性 T 细胞 (Treg) 浸润到肿瘤中来增强小鼠肿瘤的生长和转移。理论上，P-选择素拮抗剂可以抑制这一过程。海藻酸丙二醇酯硫酸钠（PSS）是一种肝素类海洋药物，最初在中国被批准用于治疗心血管疾病。此前，我们报道 PSS 是一种有效的体外 P-选择素拮抗剂。然而，PSS是否能够在体内调节Treg浸润及其对肺转移的影响尚不清楚。我们的结果表明，30mg/kg 的 PSS 显着抑制肺转移并提高总体生存率，其效力与阳性对照 LMWH 相当。机理研究表明，PSS通过直接与活化血小板的P-选择素结合来阻断肿瘤细胞粘附并活化血小板。与模型组相比，PSS治疗21天后，肺部Tregs的百分比降低了63%，同时增加了CD8 T细胞（1.59倍）和颗粒酶B CD8 T细胞（2.08倍）的百分比，以产生适应性反应用于全身性肿瘤抑制。研究表明，P-选择素拮抗剂 PSS 通过抑制调节性 T 细胞 (Treg) 浸润肿瘤来抑制肺转移。版权所有 © 2024。由 Elsevier B.V. 出版。

P-selectin has been shown to enhance growth and metastasis of mouse tumors by promoting regulatory T cell (Treg) infiltration into the tumors. Theoretically, a P-selectin antagonist could suppress the process. Popylene glycol alginate sodium sulfate (PSS) is a heparin-like marine drug, which was originally approved to treat cardiovascular disease in China. Previously, we reported that PSS was an effective P-selectin antagonist in vitro. However, it is unknown whether PSS can regulate Treg infiltration and its effect on lung metastasis in vivo. Our results showed that PSS at 30 mg/kg significantly suppressed lung metastasis and improved overall survival, with potency comparable to the positive control LMWH. Mechanistic study indicated that PSS blocked tumor cells adhesion and activated platelets by directly binding with activated platelet's P-selectin. Compared to the model group, PSS decreased the percent of Tregs by 63 % in lungs after treating for 21 days while increasing CD8+ T cells (1.59-fold) and Granzyme B+ CD8 T cells (2.08-fold)' percentage for generating an adaptive response for systemic tumor suppression. The study indicated that the P-selectin antagonist, PSS, suppressed lung metastasis by inhibiting the infiltration of regulatory T cells (Treg) into the tumors.Copyright © 2024. Published by Elsevier B.V.