Low molecular weight fucoidan LF2 improves the immunosuppressive tumor microenvironment and enhances the anti-pancreatic cancer activity of oxaliplatin - 22/03/24
Abstract |
Chemotherapy remains the cornerstone of pancreatic cancer treatment. However, the dense interstitial and immunosuppressive microenvironment frequently render the ineffective anti-tumor activity of chemotherapeutic agents. Macrophages play a key role in the tumor immunomodulation. In this study, we found that low molecular weight of fucoidan (LF2) directly regulated the differentiation of mononuclear macrophages into the CD86+ M1 phenotype. LF2 significantly upregulated the expressions of M1 macrophage-specific cytokines, including iNOS, IL-6, TNFα and IL-12. LF2 modulated macrophage phenotypic transformation through activation of TLR4-NFκB pathway. Furthermore, we observed that LF2 enhanced the pro-apoptotic activity of oxaliplatin (OXA) in vitro by converting macrophages to a tumoricidal M1 phenotype. Meanwhile, LF2 increased intratumoral M1 macrophage infiltration and ameliorated the immunosuppressed tumor microenvironment, which in turn enhanced the anti-pancreatic ductal adenocarcinoma (PDAC) activity of OXA in vivo. Taken together, our results suggested that LF2 could act as a TLR4 agonist targeting macrophages and has a synergistic effect against PDAC when combined with OXA.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | LF2 programmed mononuclear macrophages to M1 phenotype. |
• | LF2-polarized M1 macrophages enhanced the pro-apoptosis activity of oxaliplatin. |
• | LF2 polarized macrophages to M1 phenotype by activating TLR4-NFκB signaling axis. |
• | LF2 improved the immunosuppressed tumor microenvironment in vivo. |
• | LF2 enhanced the anticancer activity of oxaliplatin in vivo. |
Keywords : Fucoidan, Tumor microenvironment, Macrophages, Oxaliplatin
Plan
Vol 173
Article 116360- avril 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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