{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:30:10Z","timestamp":1786116610610,"version":"build-2736575974"},"reference-count":108,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Immune checkpoint inhibitors (ICIs) have redefined the treatment landscape of advanced malignancies, yet primary and acquired resistance severely limits their therapeutic efficacy across most solid tumors. Even in biomarker-stratified patient cohorts, objective response rates frequently fall below 25%. Natural polysaccharides have emerged as a unique category of immune adjuvants. Beyond activating innate immune receptors including Toll-like receptor 4 and downstream MyD88 signaling, such macromolecules remodel the gut microbiota\u2013metabolite axis and partially reverse immunosuppressive tumor microenvironments. Cumulative preclinical findings and early-phase clinical observations suggest synergistic therapeutic benefits for polysaccharide plus ICI combinations. Still, robust evidence from large-scale randomized Phase III trials remains absent, and polysaccharides cannot yet be validated as standard adjuvants to resolve ICI resistance. In this review, we systematically dissect the structural basis governing polysaccharide immunomodulation and elaborate four core mechanisms for overcoming immunotherapy resistance: repolarizing tumor-associated macrophages toward anti-tumor phenotypes, alleviating CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell exhaustion, regulating bidirectional gut microbiota-immune crosstalk, and inhibiting tumor-intrinsic immune escape cascades. We further summarize persistent translational bottlenecks: structural heterogeneity, nonstandard quality control, low oral bioavailability, and inconsistent clinical trial protocols, and conduct a head-to-head comparison between polysaccharides and mainstream immunostimulants (CpG oligodeoxynucleotides, STING agonists, fecal microbiota transplantation). Advanced technical tools including AI-assisted glycomics and graph neural networks, alongside synthetic biology platforms, provide new solutions to resolve structural identification and mass-production limitations. Integrating polysaccharide production with Industry 6.0 intelligent manufacturing and circular bioeconomy models can balance therapeutic development and global sustainable development targets. Finally, we propose a precision medicine workflow incorporating multi-layer biomarkers (gut microbial profiles, intratumoral immune signatures, glycomic fingerprints) to optimize patient stratification and individualized dosing. Rather than presenting rigid standardized treatment schemes, this review constructs a realistic, mechanism-guided roadmap to accelerate the clinical translation of natural polysaccharide ICI adjuvants.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1914914","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T11:36:51Z","timestamp":1786016211000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural polysaccharides as immune adjuvants to overcome immune checkpoint inhibitor resistance: mechanistic insights, clinical evidence, and translational challenges"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuhua","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]},{"name":"Department of Pharmacy, The First Naval Hospital of Southern Theatre Command","place":["Zhanjiang, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Changhai Hospital, Naval Military Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shurong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Naval Hospital of Southern Theatre Command","place":["Zhanjiang, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, No. 971 Hospital of the People\u2019s Liberation Army Navy","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1703481","article-title":"Immune-related adverse events associated with immune checkpoint blockade","volume":"378","author":"Postow","year":"2018","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41408-021-00459-7","article-title":"CAR-T cell therapy: current limitations and potential strategies","volume":"11","author":"Sterner","year":"2021","journal-title":"Blood Cancer J"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-321031","article-title":"Ginseng polysaccharides alter the gut microbiota and kynurenine\/tryptophan ratio, potentiating the antitumour effect of anti-PD-1\/PD-L1 immunotherapy","volume":"71","author":"Huang","year":"2022","journal-title":"Gut"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.137043","article-title":"A review on structure, bioactivity, mechanism, structure-activity relationship and application of anti-breast cancer polysaccharides","volume":"282","author":"Wang","year":"2024","journal-title":"Int J Biol Macromol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12632","article-title":"Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity","volume":"7","author":"Li","year":"2016","journal-title":"Nat Commun"},{"key":"B6","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.ccell.2019.06.008","article-title":"Removal of N-linked glycosylation enhances PD-L1 detection and predicts anti-PD-1\/PD-L1 therapeutic efficacy","volume":"36","author":"Lee","year":"2019","journal-title":"Cancer Cell"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-0099","article-title":"STK11\/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma","volume":"8","author":"Skoulidis","year":"2018","journal-title":"Cancer Discov"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2019.10.004","article-title":"Nivolumab monotherapy and nivolumab plus ipilimumab in recurrent small cell lung cancer: results from the CheckMate 032 randomized cohort","volume":"15","author":"Ready","year":"2020","journal-title":"J Thorac Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102463","article-title":"Inhibition of APOC1\u00a0promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencing","volume":"56","author":"Hao","year":"2022","journal-title":"Redox Biol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00661-4","article-title":"Gut microbiota-derived metabolites in the regulation of host immune responses and immune-related inflammatory diseases","volume":"18","author":"Yang","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/nu9121348","article-title":"Short chain fatty acids in the colon and peripheral tissues: a focus on butyrate, colon cancer, obesity and insulin resistance","volume":"9","author":"McNabney","year":"2017","journal-title":"Nutrients"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan3706","article-title":"Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors","volume":"359","author":"Routy","year":"2018","journal-title":"Science"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb5920","article-title":"Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients","volume":"371","author":"Baruch","year":"2021","journal-title":"Science"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac4255","article-title":"Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy","volume":"350","author":"Sivan","year":"2015","journal-title":"Science"},{"key":"B15","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1007\/s00262-025-03986-5","article-title":"NSUN2\/ALYREF axis-driven m5C methylation enhances PD-L1 expression and facilitates immune evasion in non-small-cell lung cancer","volume":"74","author":"Yang","year":"2025","journal-title":"Cancer Immunol Immunother"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-008190","article-title":"Association of metabolomics with PD-1 inhibitor plus chemotherapy outcomes in patients with advanced NSCLC","volume":"12","author":"Zheng","year":"2024","journal-title":"J Immunother Cancer"},{"key":"B17","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/nri1748","article-title":"Dectin-1: a signalling non-TLR pattern-recognition receptor","volume":"6","author":"Brown","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2023.120746","article-title":"Naturally and chemically acetylated polysaccharides: structural characteristics, synthesis, activities, and applications","volume":"313","author":"Li","year":"2023","journal-title":"Carbohydr Polym"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2025.124618","article-title":"A structurally distinct arabinose-bridged arabinogalactan from Lycium barbarum as a TLR4-activating adjuvant for nanovaccine-based cancer immunotherapy","volume":"373","author":"Bao","year":"2026","journal-title":"Carbohydr Polym"},{"key":"B20","doi-asserted-by":"publisher","first-page":"13440","DOI":"10.1038\/s41598-025-97423-3","article-title":"Immunostimulatory effects mechanism of polysaccharide extracted from Acanthopanax senticosus on RAW 264.7 cells through activating the TLR\/MAPK\/NF-\u03baB signaling pathway","volume":"15","author":"Wang","year":"2025","journal-title":"Sci Rep"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2025.123695","article-title":"Novel galactose-rich polysaccharide from Ganoderma lucidum: structural characterization and immunomodulatory activities","volume":"362","author":"Wu","year":"2025","journal-title":"Carbohydr Polym"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.132671","article-title":"Hyaluronic acid-conjugated methotrexate and 5-fluorouracil for targeted drug delivery","volume":"273","author":"Shao","year":"2024","journal-title":"Int J Biol Macromol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.146940","article-title":"Structural elucidation, gut fermentation, and immunomodulatory mechanisms of \u03b2-glucan polymorphs","volume":"322","author":"Huo","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2025.146468","article-title":"Mushroom beta-glucans as immunomodulators: elucidation of structure-function relationship","volume":"495","author":"Dilrukshi","year":"2025","journal-title":"Food Chem"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.12.040","article-title":"Process-Programmed Extraction-Structure-Activity Relationships (ESAR) in edible and medicinal mushroom polysaccharides: a mechanistic and application-oriented framework","author":"Zhao","year":"2025","journal-title":"J Adv Res"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202401167","article-title":"The structure characterization of polysaccharides from Codonopsis pilosula and the structure-activity relationship with immune-regulation on THP-1 cells","volume":"22","author":"Fu","year":"2025","journal-title":"Chem Biodivers"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-00375-4","article-title":"Dietary fibre in gastrointestinal health and disease","volume":"18","author":"Gill","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106141","article-title":"Bacteroides fragilis prevents aging-related atrial fibrillation in rats via regulatory T cells-mediated regulation of inflammation","volume":"177","author":"Zhang","year":"2022","journal-title":"Pharmacol Res"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.148071","article-title":"Review on seaweed derived sulfated and non-sulfated marine polysaccharides as multifunctional food ingredients: Structure-function relationships, bioactivities and applications in functional foods","volume":"330","author":"John","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.2174\/0118715206435063260413064006","article-title":"Fungal \u03b2-D-glucans: versatile agents in immune modulation, tumor suppression, and nanomedicine advances","author":"Jin","year":"2026","journal-title":"Anticancer Agents Med Chem"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2023.121036","article-title":"Structure-activity relationship of low molecular weight Astragalus membranaceus polysaccharides produced by Bacteroides","volume":"316","author":"Cai","year":"2023","journal-title":"Carbohydr Polym"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3390\/ph16060895","article-title":"Isolation, purification, and structural characterization of polysaccharides from codonopsis pilosula and their anti-tumor bioactivity by immunomodulation","volume":"16","author":"Li","year":"2023","journal-title":"Pharm (Basel)"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3390\/foods11162470","article-title":"Effects of ultrasound modification with different frequency modes on the structure, chain conformation, and immune activity of polysaccharides from lentinus edodes","volume":"11","author":"Yu","year":"2022","journal-title":"Foods"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2021.06.122","article-title":"Ganoderma lucidum: A potential source to surmount viral infections through \u03b2-glucans immunomodulatory and triterpenoids antiviral properties","volume":"187","author":"Ahmad","year":"2021","journal-title":"Int J Biol Macromol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3390\/nu16111654","article-title":"Comparative study on the mechanism of macrophage activation induced by polysaccharides from fresh and dried longan","volume":"16","author":"Wang","year":"2024","journal-title":"Nutrients"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.761641","article-title":"Safflower polysaccharide inhibits AOM\/DSS-induced mice colorectal cancer through the regulation of macrophage polarization","volume":"12","author":"Wang","year":"2021","journal-title":"Front Pharmacol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6696606","article-title":"Ganoderma lucidum spore polysaccharide inhibits the growth of hepatocellular carcinoma cells by altering macrophage polarity and induction of apoptosis","volume":"2021","author":"Song","year":"2021","journal-title":"J Immunol Res"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.141013","article-title":"Activation of IL-2\/IL-2R pathway by Hedyotis diffusa polysaccharide improves immunotherapy in colorectal cancer","volume":"306","author":"Bai","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116172","article-title":"Astragalus polysaccharide ameliorates CD8+ T cell dysfunction through STAT3\/Gal-3\/LAG3 pathway in inflammation-induced colorectal cancer","volume":"171","author":"Li","year":"2024","journal-title":"BioMed Pharmacother"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.143323","article-title":"Chinese yam polysaccharide enhances anti-PD-1 immunotherapy in colorectal cancer through alterations in the gut microbiota and metabolites","volume":"310","author":"Zhang","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.08.020","article-title":"Emerging role of natural products in cancer immunotherapy","volume":"12","author":"Dong","year":"2022","journal-title":"Acta Pharm Sin B"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.117401","article-title":"Astragalus polysaccharide enhances antitumoral effects of chimeric antigen receptor-engineered (CAR) T cells by increasing CD122+CXCR3+PD-1- memory T cells","volume":"179","author":"Zhang","year":"2024","journal-title":"BioMed Pharmacother"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.142015","article-title":"Ginseng polysaccharides ameliorate colorectal tumorigenesis through Lachnospiraceae-mediated immune modulation","volume":"307","author":"Zong","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2023.2276814","article-title":"Modulating the gut microbiota is involved in the effect of low-molecular-weight Glycyrrhiza polysaccharide on immune function","volume":"15","author":"Song","year":"2023","journal-title":"Gut Microbes"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2024.122829","article-title":"Astragalus polysaccharides alleviate DSS-induced ulcerative colitis in mice by restoring SCFA production and regulating Th17\/Treg cell homeostasis in a microbiota-dependent manner","volume":"349","author":"Zhang","year":"2025","journal-title":"Carbohydr Polym"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.7150\/thno.54476","article-title":"Pectin supplement significantly enhanced the anti-PD-1 efficacy in tumor-bearing mice humanized with gut microbiota from patients with colorectal cancer","volume":"11","author":"Zhang","year":"2021","journal-title":"Theranostics"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3390\/foods14030387","article-title":"Polysaccharides from sea cucumber (Stichopus japonicus) synergize with anti-PD1 immunotherapy to reduce MC-38 tumor burden in mice through shaping the gut microbiome","volume":"14","author":"Li","year":"2025","journal-title":"Foods"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3390\/foods12203809","article-title":"The potential hypoglycemic competence of low molecular weight polysaccharides obtained from laminaria japonica","volume":"12","author":"Tong","year":"2023","journal-title":"Foods"},{"key":"B49","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1007\/s00262-025-04118-9","article-title":"Gut modulation to regulate NF-\u03baB in colorectal and gastric cancer therapy and inflammation","volume":"74","author":"Kearns","year":"2025","journal-title":"Cancer Immunol Immunother"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-04186-5","article-title":"Fecal microbiota transplantation plus immunotherapy in non-small cell lung cancer and melanoma: the phase 2 FMT-LUMINate trial","volume":"32","author":"Duttagupta","year":"2026","journal-title":"Nat Med"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1039\/d3fo04807a","article-title":"Fucoidan enhances the anti-tumor effect of anti-PD-1 immunotherapy by regulating gut microbiota","volume":"15","author":"Li","year":"2024","journal-title":"Food Funct"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-022-00631-9","article-title":"Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms","volume":"19","author":"Cani","year":"2022","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01694-6","article-title":"Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial","volume":"28","author":"Dizman","year":"2022","journal-title":"Nat Med"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2024.100741","article-title":"The effect and mechanism of astragalus polysaccharides on T cells and macrophages in inhibiting prostate cancer","volume":"48","author":"Wu","year":"2025","journal-title":"BioMed J"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2022.2112963","article-title":"Astragalus polysaccharide attenuated PD-L1-mediated immunosuppression via miR-133a-3p\/MSN axis in HCC","volume":"60","author":"He","year":"2022","journal-title":"Pharm Biol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S294253","article-title":"Actinidia eriantha polysaccharide and PD1-antibody combination therapy enhances antitumor efficacy in colorectal cancer-xenograft mice","volume":"14","author":"Li","year":"2021","journal-title":"Onco Targets Ther"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajps.2021.07.004","article-title":"Spatiotemporally co-delivery of triple therapeutic drugs via HA-coating nanosystems for enhanced immunotherapy","volume":"16","author":"Ma","year":"2021","journal-title":"Asian J Pharm Sci"},{"key":"B58","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1186\/s12951-025-03708-0","article-title":"Astragalus polysaccharide-based nano-platforms loading PTX to boost chemo-immunotherapy for triple-negative breast cancer with intrinsic GLUT-targeting ability and immunoregulatory activity","volume":"23","author":"Lan","year":"2025","journal-title":"J Nanobiotechnol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s12865-024-00651-x","article-title":"\u03b2-glucan combined with Envafolimab and Endostar as immune rechallenge for metastatic non-small cell lung cancer","volume":"25","author":"Geng","year":"2024","journal-title":"BMC Immunol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.887457","article-title":"\u03b2-Glucan combined with PD-1\/PD-L1 checkpoint blockade for immunotherapy in patients with advanced cancer","volume":"13","author":"Wang","year":"2022","journal-title":"Front Pharmacol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1097\/XCS.0000000000001291","article-title":"Irreversible electroporation combined with \u03b2-glucan in pancreatic cancer","volume":"240","author":"Martin","year":"2025","journal-title":"J Am Coll Surg"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.135922","article-title":"Fucoidan from Durvillaea Antarctica enhances the anti-cancer effect of anti-PD-L1 antibody by activating dendritic cells and T cells","volume":"280","author":"Zhang","year":"2024","journal-title":"Int J Biol Macromol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-022-03276-4","article-title":"PD-L1 antibody enhanced \u03b2-glucan antitumor effects via blockade of immune checkpoints in a melanoma model","volume":"72","author":"Hu","year":"2023","journal-title":"Cancer Immunol Immunother"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.3c08385","article-title":"Ganoderma lucidum polysaccharide supplementation significantly activates T-cell-mediated antitumor immunity and enhances anti-PD-1 immunotherapy efficacy in colorectal cancer","volume":"72","author":"Li","year":"2024","journal-title":"J Agric Food Chem"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202404347","article-title":"Manipulating the crosstalk between cancer and immunosuppressive cells with phototherapeutic gold-nanohut for reprogramming tumor microenvironment","volume":"11","author":"Cheng","year":"2024","journal-title":"Adv Sci"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-1012","article-title":"Phase I trial of a bivalent gangliosides vaccine in combination with \u03b2-glucan for high-risk neuroblastoma in second or later remission","volume":"20","author":"Kushner","year":"2014","journal-title":"Clin Cancer Res"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2021.05.120","article-title":"Radix Astragali polysaccharide RAP directly protects hematopoietic stem cells from chemotherapy-induced myelosuppression by increasing FOS expression","volume":"183","author":"Bao","year":"2021","journal-title":"Int J Biol Macromol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1605488","article-title":"Lentinan enhances CAR-T cell potency in solid tumors by optimizing T cell differentiation","volume":"16","author":"Niu","year":"2025","journal-title":"Front Immunol"},{"key":"B69","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s13046-023-02649-6","article-title":"First-in-human phase 1 clinical trial of anti-core 1 O-glycans targeting monoclonal antibody NEO-201 in treatment-refractory solid tumors","volume":"42","author":"Cole","year":"2023","journal-title":"J Exp Clin Cancer Res"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01698-2","article-title":"Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1","volume":"28","author":"McCulloch","year":"2022","journal-title":"Nat Med"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2022.2081010","article-title":"Clostridium butyricum therapy restores the decreased efficacy of immune checkpoint blockade in lung cancer patients receiving proton pump inhibitors","volume":"11","author":"Tomita","year":"2022","journal-title":"Oncoimmunology"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1186\/s12865-025-00681-z","article-title":"\u03b2-Glucan induced plasma B cells differentiation to enhance antitumor immune responses by Dectin-1","volume":"26","author":"Bai","year":"2025","journal-title":"BMC Immunol"},{"key":"B73","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1056\/NEJMoa2109970","article-title":"Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma","volume":"386","author":"Tawbi","year":"2022","journal-title":"N\u00a0Engl J Med"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-25-0806","article-title":"Combined targeting of PD-1 and TIM-3 in patients with locally advanced or metastatic non-small cell lung cancer: AMBER part 2B","volume":"31","author":"Davar","year":"2025","journal-title":"Clin Cancer Res"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1200\/JCO-25-01346","article-title":"RP1 combined with nivolumab in advanced anti-PD-1-failed melanoma (IGNYTE)","volume":"43","author":"Wong","year":"2025","journal-title":"J Clin Oncol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtice.2018.05.039","article-title":"Effects of water culture medium, cultivation systems and growth modes for microalgae cultivation: a review","volume":"91","author":"Chew","year":"2018","journal-title":"J\u00a0Taiwan Inst Chem Eng"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1007\/s10668-025-06247-8","article-title":"Ecofriendly techniques for the sustainable degradation of synthetic plastic polymers using a bacterial hyperproducer","author":"Majeed","year":"2025","journal-title":"Environ Dev Sustain"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3390\/md23110412","article-title":"Seaweed polysaccharides: a rational approach for food safety studies","volume":"23","author":"Cotas","year":"2025","journal-title":"Mar Drugs"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1147641","article-title":"Immunomodulatory function and anti-tumor mechanism of natural polysaccharides: a review","volume":"14","author":"Yang","year":"2023","journal-title":"Front Immunol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1641928","article-title":"Preparation, structural characteristics and immune regulatory effects of Codonopsis pilosula polysaccharides: a review","volume":"16","author":"Pan","year":"2025","journal-title":"Front Immunol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1111\/1541-4337.13244","article-title":"Exploring the partial degradation of polysaccharides: structure, mechanism, bioactivities, and perspectives","volume":"22","author":"Chen","year":"2023","journal-title":"Compr Rev Food Sci Food Saf"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2023.126484","article-title":"Preclinical pharmacokinetics-related pharmacological effects of orally administered polysaccharides from traditional Chinese medicines: a review","volume":"252","author":"Ye","year":"2023","journal-title":"Int J Biol Macromol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2021.103434","article-title":"Rechallenge of immune checkpoint inhibitors: a systematic review and meta-analysis","volume":"165","author":"Inno","year":"2021","journal-title":"Crit Rev Oncol Hematol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30074-8","article-title":"iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics","volume":"18","author":"Seymour","year":"2017","journal-title":"Lancet Oncol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-007080","article-title":"Low molecular weight heparin synergistically enhances the efficacy of adoptive and anti-PD-1-based immunotherapy by increasing lymphocyte infiltration in colorectal cancer","volume":"11","author":"Quan","year":"2023","journal-title":"J Immunother Cancer"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2025.217616","article-title":"Clinical development of immuno-oncology therapeutics","volume":"617","author":"Wang","year":"2025","journal-title":"Cancer Lett"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.3390\/md23040177","article-title":"Exploring the in vivo fate of \u03b2-1,3\/1,6-glucan using quantitative tandem mass spectrometry based on a structure-specific fragment","volume":"23","author":"Xu","year":"2025","journal-title":"Mar Drugs"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.7506\/spkx1002-6630-20251106-048","article-title":"Research progress on green manufacturing technologies for polysaccharides","volume":"47","author":"Ji","year":"2026","journal-title":"Shipin Kexue (Food Science)"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e23593","article-title":"The traditional use, structure, and immunostimulatory activity of bioactive polysaccharides from traditional Chinese root medicines: a review","volume":"10","author":"Bo","year":"2023","journal-title":"Heliyon"},{"key":"B90","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-032-07278-8_5","article-title":"Sustainable IoT working in cloud, data infrastructure and security in Industry 6.0","volume-title":"Intelligent Manufacturing in Industry 6.0","author":"Majeed","year":"2026"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163536","article-title":"Quantitative structure activity relationship models for the antioxidant activity of polysaccharides","volume":"11","author":"Li","year":"2016","journal-title":"PloS One"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adx6373","article-title":"Atom-level machine learning of protein-glycan interactions and cross-chiral recognition in glycobiology","volume":"11","author":"Carpenter","year":"2025","journal-title":"Sci Adv"},{"key":"B93","doi-asserted-by":"publisher","first-page":"3755","DOI":"10.1038\/s41467-024-48193-5","article-title":"Biosynthetic production of\u00a0anticoagulant heparin polysaccharides through metabolic and sulfotransferases engineering strategies","volume":"15","author":"Deng","year":"2024","journal-title":"Nat Commun"},{"key":"B94","doi-asserted-by":"publisher","first-page":"13012","DOI":"10.1038\/s41598-026-46439-4","article-title":"Transfer of the synechan biosynthesis and regulatory pathway enables sulfated polysaccharide production in Synechococcus elongatus PCC 7942","volume":"16","author":"Maeda","year":"2026","journal-title":"Sci Rep"},{"key":"B95","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1038\/s41467-026-68579-x","article-title":"Large-scale serum N-glycomics tracks N-glycosylation dynamics in hepatocellular carcinoma progression and enables early diagnosis","volume":"17","author":"Fu","year":"2026","journal-title":"Nat Commun"},{"key":"B96","doi-asserted-by":"publisher","first-page":"7075","DOI":"10.1038\/s41467-025-61473-y","article-title":"Development and application of GlycanDIA workflow for glycomic analysis","volume":"16","author":"Xie","year":"2025","journal-title":"Nat Commun"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2025.112162","article-title":"Enriched pathways in gut microbiome predict response to immune checkpoint inhibitor treatment across demographic regions and various cancer types","volume":"28","author":"Cai","year":"2025","journal-title":"iScience"},{"key":"B98","doi-asserted-by":"publisher","first-page":"3075","DOI":"10.1038\/s41467-024-47425-y","article-title":"Molecular patterns of resistance to immune checkpoint blockade in melanoma","volume":"15","author":"Lauss","year":"2024","journal-title":"Nat Commun"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01655-5","article-title":"Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer","volume":"28","author":"Derosa","year":"2022","journal-title":"Nat Med"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c08898","article-title":"In silico-guided discovery of polysaccharide derivatives as adjuvants in nanoparticle vaccines for cancer immunotherapy","volume":"19","author":"Cui","year":"2025","journal-title":"ACS Nano"},{"key":"B101","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1186\/s12951-023-01989-x","article-title":"Nanovaccine-based strategies for lymph node targeted delivery and imaging in tumor immunotherapy","volume":"21","author":"He","year":"2023","journal-title":"J Nanobiotechnol"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2019.115128","article-title":"Polyethylenimine-coated PLGA nanoparticles-encapsulated Angelica sinensis polysaccharide as an adjuvant to enhance immune responses","volume":"223","author":"Gu","year":"2019","journal-title":"Carbohydr Polym"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinsp.2025.100805","article-title":"\u03b2-glucan combined with PD-1\/PD-L1 checkpoint blockade suppresses pancreatic tumor growth after ablation therapy","volume":"80","author":"Wu","year":"2025","journal-title":"Clinics"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2024.124835","article-title":"Fabrication and\u00a0evaluation of chitosan-coated nanostructured lipid carriers for co-delivery of paclitaxel and PD-L1 siRNA","volume":"666","author":"Kim","year":"2024","journal-title":"Int J Pharm"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2023.05.016","article-title":"All-in-one glycol chitosan nanoparticles for co-delivery of doxorubicin and anti-PD-L1 peptide in cancer immunotherapy","volume":"28","author":"Song","year":"2023","journal-title":"Bioact Mater"},{"key":"B106","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.cell.2018.09.004","article-title":"Dysregulated microbial fermentation of soluble fiber induces cholestatic liver cancer","volume":"175","author":"Singh","year":"2018","journal-title":"Cell"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-025-02597-w","article-title":"Turn cold tumors hot by reprogramming the tumor microenvironment","volume":"43","author":"Yuan","year":"2025","journal-title":"Nat Biotechnol"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.32604\/or.2025.066805","article-title":"Igniting cold tumors: multi-omics-driven strategies to overcome immune evasion and restore immune surveillance","volume":"33","author":"Huang","year":"2025","journal-title":"Oncol Res"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1914914\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T11:36:54Z","timestamp":1786016214000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1914914\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,6]]},"references-count":108,"alternative-id":["10.3389\/fimmu.2026.1914914"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1914914","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,6]]},"article-number":"1914914"}}