Anti-Proliferative and Pro-Apoptotic vLMW Fucoidan Formulas Decrease PD-L1 Surface Expression in EBV Latency III and...

Area of Science:

• Immunology
• Oncology
• Pharmacology

Background:

• Epstein-Barr virus (EBV) infects most of the global population, causing B-cell immortalization and association with lymphomas.
• Lymphoblastoid cell lines (LCLs) and diffuse large B-cell lymphomas (DLBCLs) overexpress programmed death-ligand 1 (PD-L1), an immune checkpoint that inhibits anti-tumoral T-cell responses.
• Current immunotherapies targeting PD-L1/PD-1 interactions have dose-dependent toxicities, necessitating alternative strategies to improve efficacy.

Purpose of the Study:

• To investigate the potential of fucoidan, a seaweed polysaccharide, in modulating PD-L1 expression in EBV-associated B-cell malignancies.
• To evaluate the anti-proliferative and pro-apoptotic effects of native and very-low-molecular-weight fucoidan (vLMW-F) on LCLs and DLBCLs.
• To explore vLMW-F as a potential adjuvant therapy to enhance immunotherapy by reducing PD-L1 expression.

Main Methods:

• LCLs and DLBCLs were treated with native fucoidan (from *Fucus vesiculosus*) and vLMW-F formulations.
• Cell proliferation, apoptosis, and PD-L1 expression (transcriptional and surface levels) were assessed.
• Effects on normal B- and T-cells were evaluated to determine toxicity.

Main Results:

• vLMW-F significantly decreased cell proliferation and increased apoptosis in LCLs and DLBCLs, without toxicity to normal B- and T-cells.
• Both native fucoidan and vLMW-F reduced PD-L1 expression, with vLMW-F showing greater efficacy.
• Decreased PD-L1 expression was potentially linked to alterations in the actin network, affecting secretory vesicle fusion with the plasma membrane.

Conclusions:

• vLMW-F exhibits significant anti-proliferative and pro-apoptotic effects on lymphoma cells.
• vLMW-F effectively reduces PD-L1 surface expression, suggesting a mechanism involving actin cytoskeleton modulation.
• vLMW-F holds promise as an adjuvant therapy to improve the efficacy of current immunotherapies for EBV-associated B-cell lymphomas.