{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T13:02:54Z","timestamp":1785762174735,"version":"3.56.0"},"reference-count":42,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-00552980"],"award-info":[{"award-number":["RS-2025-00552980"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2023-00207868"],"award-info":[{"award-number":["RS-2023-00207868"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2024IP0017-2"],"award-info":[{"award-number":["2024IP0017-2"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Asan Medical Center","award":["RS-2025-00552980"],"award-info":[{"award-number":["RS-2025-00552980"]}]},{"name":"Asan Medical Center","award":["RS-2023-00207868"],"award-info":[{"award-number":["RS-2023-00207868"]}]},{"name":"Asan Medical Center","award":["2024IP0017-2"],"award-info":[{"award-number":["2024IP0017-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Various studies have demonstrated fucoidan\u2019s immunomodulatory effects. A previous study reported the anticancer effects of Durvillaea antarctica fucoidan (DAF) via immune activation in mice. Methods: In this study, we confirmed the DAF\u2019s pulmonary immune activation ability by nasal administration of the dendritic cells (DCs) and T cells. Furthermore, we examined its ability to enhance the efficacy of lung cancer treatment by combining it with anti-PD-L1 antibodies to activate the lung immune response. Results: Nasal DAF administration increased C-C chemokine receptor type 7 expression in DCs and promoted DC migration to the mediastinal lymph nodes (mLN). Specifically, DAF increased conventional DC type 1 (cDC1) and cDC2 numbers in mLN and potently activated cDC1. Furthermore, the nasal administration of DAF increased the production of inflammatory cytokines in the lungs and peripheral blood. Repeated intranasal administration of DAF induced T-cell activation, resulting in the enhanced production of interferon-gamma and tumor necrosis factor-alpha in CD4 T and CD8 T cells. CD8 T cells also showed increased secretion of cytotoxic mediators after DAF treatment, and the proportion of Tregs expressing FoxP3 decreased in the mLN. DAF inhibited lung cancer growth in Lewis lung carcinoma 2 cells, which was enhanced by combining it with an anti-programmed death-ligand 1 antibody. Finally, the anticancer effects of DAF were not observed in mice with depleted CD4-positive and CD8-positive cells. Conclusions: Nasal administration of DAF may inhibit lung cancer growth by inducing lung immune activation and is expected to be helpful as an immune activator for nasal administration.<\/jats:p>","DOI":"10.3390\/ph18091354","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T19:16:17Z","timestamp":1757445377000},"page":"1354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nasal Administration of Durvillaea antarctica Fucoidan Inhibits Lung Cancer Growth in Mice Through Immune Activation"],"prefix":"10.3390","volume":"18","author":[{"given":"Hee Sung","family":"Kim","sequence":"first","affiliation":[{"name":"Department of General Surgery, Hallym University College of Medicine, Hallym Medical Center, Anyang 14068, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2320-6365","authenticated-orcid":false,"given":"Peter C. W.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-O","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/bs.pmbts.2019.03.003","article-title":"The structures and biological functions of polysaccharides from traditional Chinese herbs","volume":"163","author":"Zeng","year":"2019","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2224751","DOI":"10.1080\/15502783.2023.2224751","article-title":"Effects of fucoidan supplementation on inflammatory and immune response after high-intensity exercise","volume":"20","author":"McFadden","year":"2023","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Jin, J.-O., Yadav, D., Madhwani, K., Puranik, N., Chavda, V., and Song, M. (2022). Seaweeds in the oncology arena: Anti-cancer potential of fucoidan as a drug\u2014A review. Molecules, 27.","DOI":"10.3390\/molecules27186032"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.carbpol.2016.08.005","article-title":"A review about the development of fucoidan in antitumor activity: Progress and challenges","volume":"154","author":"Wu","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Qin, L., Xu, H., He, Y., Liang, C., Wang, K., Cao, J., Qu, C., and Miao, J. (2022). Purification, Chemical Characterization and Immunomodulatory Activity of a Sulfated Polysaccharide from Marine Brown Algae Durvillaea antarctica. Mar. Drugs, 20.","DOI":"10.3390\/md20040223"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhang, W., Park, H.-B., An, E.-K., Kim, S.-J., Ryu, D., Kim, D., Lim, D., Hwang, J., Kwak, M., and You, S. (2024). Fucoidan from Durvillaea Antarctica enhances the anti-cancer effect of anti-PD-L1 antibody by activating dendritic cells and T cells. Int. J. Biol. Macromol., 280.","DOI":"10.1016\/j.ijbiomac.2024.135922"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zhang, W., Lee, P.C., and Jin, J.-O. (2024). Anti-Inflammatory Effect of Fucoidan from Costaria costata Inhibited Lipopolysaccharide-Induced Inflammation in Mice. Mar. Drugs, 22.","DOI":"10.3390\/md22090401"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"121899","DOI":"10.1016\/j.carbpol.2024.121899","article-title":"The STING-mediated antiviral effect of fucoidan from Durvillaea antarctica","volume":"331","author":"Li","year":"2024","journal-title":"Carbohydr. Polym."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ijbiomac.2021.06.045","article-title":"Ecklonia cava fucoidan has potential to stimulate natural killer cells in vivo","volume":"185","author":"Zhang","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Jin, J.-O., Chauhan, P.S., Arukha, A.P., Chavda, V., Dubey, A., and Yadav, D. (2021). The therapeutic potential of the anticancer activity of fucoidan: Current advances and hurdles. Mar. Drugs, 19.","DOI":"10.3390\/md19050265"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhang, W., Hwang, J., Yadav, D., An, E.-K., Kwak, M., Lee, P.C.-W., and Jin, J.-O. (2021). Enhancement of immune checkpoint inhibitor-mediated anti-cancer immunity by intranasal treatment of Ecklonia cava fucoidan against metastatic lung cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179125"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41568-023-00560-y","article-title":"Dynamics and specificities of T cells in cancer immunotherapy","volume":"23","author":"Oliveira","year":"2023","journal-title":"Nat. Rev. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"109887","DOI":"10.1016\/j.intimp.2023.109887","article-title":"Nanovaccines for cancer immunotherapy: Focusing on complex formation between adjuvant and antigen","volume":"117","author":"Goradel","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"153723","DOI":"10.1016\/j.prp.2021.153723","article-title":"Cancer immunotherapy: Challenges and limitations","volume":"229","author":"Taefehshokr","year":"2022","journal-title":"Pathol. Res. Pract."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Durgeau, A., Virk, Y., Corgnac, S., and Mami-Chouaib, F. (2018). Recent advances in targeting CD8 T-cell immunity for more effective cancer immunotherapy. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00014"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/cr.2016.157","article-title":"Dendritic cell-based immunotherapy","volume":"27","author":"Sabado","year":"2017","journal-title":"Cell Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1046\/j.1365-2567.2001.01204.x","article-title":"In vivo maturation and migration of dendritic cells","volume":"102","year":"2001","journal-title":"Immunology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/s41423-023-00990-6","article-title":"Dendritic cell subsets in cancer immunity and tumor antigen sensing","volume":"20","author":"Salvi","year":"2023","journal-title":"Cell Mol. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"You, W., Zhou, Z., Li, Z., Yan, J., and Wang, Y. (2025). From foe to friend: Rewiring oncogenic pathways through artificial selenoprotein to combat immune-resistant tumor. J. Pharm. Anal., 101322.","DOI":"10.1016\/j.jpha.2025.101322"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s10875-009-9278-8","article-title":"Cytokine-producing dendritic cells in the pathogenesis of inflammatory skin diseases","volume":"29","author":"McNutt","year":"2009","journal-title":"J. Clin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.ijbiomac.2022.03.122","article-title":"Comparison of the immune activation capacities of fucoidan and laminarin extracted from Laminaria japonica","volume":"208","author":"An","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.3390\/md13031084","article-title":"Fucoidan from Macrocystis pyrifera has powerful immune-modulatory effects compared to three other fucoidans","volume":"13","author":"Zhang","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Jin, J.-O., Zhang, W., Du, J.-Y., Wong, K.-W., Oda, T., and Yu, Q. (2014). Fucoidan can function as an adjuvant in vivo to enhance dendritic cell maturation and function and promote antigen-specific T cell immune responses. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099396"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Apostolova, E., Lukova, P., Baldzhieva, A., Katsarov, P., Nikolova, M., Iliev, I., Peychev, L., Trica, B., Oancea, F., and Delattre, C. (2020). Immunomodulatory and anti-inflammatory effects of fucoidan: A review. Polymers, 12.","DOI":"10.3390\/polym12102338"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e2","DOI":"10.4110\/in.2022.22.e2","article-title":"Immune checkpoint inhibitors in 10 years: Contribution of basic research and clinical application in cancer immunotherapy","volume":"22","author":"Lee","year":"2022","journal-title":"Immune Netw."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/bs.apha.2021.01.002","article-title":"Review of immune checkpoint inhibitors in immuno-oncology","volume":"91","author":"Jacob","year":"2021","journal-title":"Adv. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.intimp.2018.06.001","article-title":"Immune checkpoint blockade therapy for cancer: An overview of FDA-approved immune checkpoint inhibitors","volume":"62","author":"Hargadon","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s12964-021-00789-w","article-title":"Immune checkpoint inhibition for pancreatic ductal adenocarcinoma: Limitations and prospects: A systematic review","volume":"19","author":"Li","year":"2021","journal-title":"Cell Commun. Signal"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Dobosz, P., St\u0119pie\u0144, M., Golke, A., and Dzieci\u0105tkowski, T. (2022). Challenges of the immunotherapy: Perspectives and limitations of the immune checkpoint inhibitor treatment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052847"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Liang, Y., Wang, L., Ma, P., Ju, D., Zhao, M., and Shi, Y. (2023). Enhancing anti-tumor immune responses through combination therapies: Epigenetic drugs and immune checkpoint inhibitors. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1308264"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1016\/j.immuni.2023.08.014","article-title":"Dendritic cells as shepherds of T cell immunity in cancer","volume":"56","author":"Pittet","year":"2023","journal-title":"Immunity"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1126\/science.8097337","article-title":"IL-12: Initiation cytokine for cell-mediated immunity","volume":"260","author":"Scott","year":"1993","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zayed, A., Al-Saedi, D.A., Mensah, E.O., Kanwugu, O.N., Adadi, P., and Ulber, R. (2023). Fucoidan\u2019s Molecular Targets: A Comprehensive Review of Its Unique and Multiple Targets Accounting for Promising Bioactivities Supported by In Silico Studies. Mar. Drugs, 22.","DOI":"10.3390\/md22010029"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lin, Z., Tan, X., Zhang, Y., Li, F., Luo, P., and Liu, H. (2020). Molecular targets and related biologic activities of fucoidan: A review. Mar. Drugs, 18.","DOI":"10.3390\/md18080376"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e343","DOI":"10.1002\/mco2.343","article-title":"Hot and cold tumors: Immunological features and the therapeutic strategies","volume":"4","author":"Wang","year":"2023","journal-title":"MedComm"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.21037\/tlcr-24-811","article-title":"Fluorofenidone enhances cisplatin efficacy in non-small cell lung cancer: A novel approach to inhibiting cancer progression","volume":"13","author":"Wang","year":"2024","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.cancergen.2024.04.001","article-title":"CircMYBL1 suppressed acquired resistance to osimertinib in non-small-cell lung cancer","volume":"284","author":"Li","year":"2024","journal-title":"Cancer Genet."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Ouyang, P., Wang, L., Wu, J., Tian, Y., Chen, C., Li, D., Yao, Z., Chen, R., Xiang, G., and Gong, J. (2024). Overcoming cold tumors: A combination strategy of immune checkpoint inhibitors. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1344272"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jad.2007.02.018","article-title":"Imbalance between pro-inflammatory and anti-inflammatory cytokines in bipolar disorder","volume":"104","author":"Kim","year":"2007","journal-title":"J. Affect. Disord."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.cyto.2016.06.003","article-title":"The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells","volume":"85","author":"Pourgholaminejad","year":"2016","journal-title":"Cytokine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"156420","DOI":"10.1016\/j.cyto.2023.156420","article-title":"Cytokine storm in COVID-19 and malaria: Annals of pro-inflammatory cytokines","volume":"173","author":"Qidwai","year":"2024","journal-title":"Cytokine"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Jarczak, D., and Nierhaus, A. (2022). Cytokine storm\u2014Definition, causes, and implications. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911740"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/9\/1354\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:42:53Z","timestamp":1760035373000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/9\/1354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,9]]},"references-count":42,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ph18091354"],"URL":"https:\/\/doi.org\/10.3390\/ph18091354","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,9]]}}}