Epstein-Barr病毒（EBV）感染全球人口的95％，并潜伏于体内。它使B细胞不退化，与淋巴瘤有关。淋巴母细胞系列（LCLs，EBV潜伏期III B细胞）通过PD-L1过度表达（编程死亡配体1免疫检查点）抑制抗肿瘤T细胞反应。许多癌细胞，包括一些弥漫性大B细胞淋巴瘤（DLBCLs），也过度表达PD-L1。免疫治疗基于抑制PD-L1 / PD-1相互作用，但存在某些剂量依赖性毒性。我们旨在通过降低PD-L1表达来寻找提高其效率的新策略。海藻酸，从棕色海藻中提取的多糖，根据其聚合度具有免疫调节和抗肿瘤活性，但在淋巴瘤细胞或免疫检查点方面的数据很少。我们用本土海藻酸（鲍鱼草）或原始的超低分子量海藻酸配方（vLMW-F）处理了LCLs和DLBCLs细胞。我们观察到细胞增殖的减少，并且vLMW-F与细胞凋亡的诱导增加，对正常B和T细胞没有毒性。我们强调了转录和PD-L1表面表达的降低，vLMW比本地海藻酸更有效。这可以通过肌动蛋白网络改变来解释，表明携带PD-L1的分泌小泡与质膜的融合较低。我们建议vLMW-F作为免疫治疗的潜在辅助剂，因为它们具有抗增殖和促凋亡的效果，并且能够降低PD-L1膜表达。

Epstein-Barr virus (EBV) infects 95% of the world's population and persists latently in the body. It immortalizes B-cells and is associated with lymphomas. LCLs (lymphoblastoid cell lines, EBV latency III B-cells) inhibit anti-tumoral T-cell response following PD-L1 overexpression (programmed death-ligand 1 immune checkpoint). Many cancer cells, including some DLBCLs (diffuse large B-cell lymphomas), also overexpress PD-L1. Immunotherapies are based on inhibition of PD-L1/PD-1 interactions but present some dose-dependent toxicities. We aim to find new strategies to improve their efficiency by decreasing PD-L1 expression. Fucoidan, a polysaccharide extracted from brown seaweed, exhibits immunomodulatory and anti-tumor activities depending on its polymerization degree, but data are scarce on lymphoma cells or immune checkpoints. LCLs and DLBCLs cells were treated with native fucoidan (Fucus vesiculosus) or original very-low-molecular-weight fucoidan formulas (vLMW-F). We observed cell proliferation decrease and apoptosis induction increase with vLMW-F and no toxicity on normal B- and T-cells. We highlighted a decrease in transcriptional and PD-L1 surface expression, even more efficient for vLMW than native fucoidan. This can be explained by actin network alteration, suggesting lower fusion of secretory vesicles carrying PD-L1 with the plasma membrane. We propose vLMW-F as potential adjuvants to immunotherapy due to their anti-proliferative and proapoptotic effects and ability to decrease PD-L1 membrane expression.