{"id":"https://openalex.org/W7203675740","doi":"https://doi.org/10.21203/rs.3.rs-10713654/v1","title":"Apigenin is a direct small-molecule inhibitor of LAG-3 that synergizes with PD-L1 blockade for cancer immunotherapy","display_name":"Apigenin is a direct small-molecule inhibitor of LAG-3 that synergizes with PD-L1 blockade for cancer immunotherapy","publication_year":2026,"publication_date":"2026-08-18","ids":{"openalex":"https://openalex.org/W7203675740","doi":"https://doi.org/10.21203/rs.3.rs-10713654/v1"},"language":"en","primary_location":{"id":"doi:10.21203/rs.3.rs-10713654/v1","doi":"https://doi.org/10.21203/rs.3.rs-10713654/v1","is_oa":true,"landing_page_url":"https://doi.org/10.21203/rs.3.rs-10713654/v1","pdf_url":"https://www.researchsquare.com/article/rs-10713654/latest.pdf","source":{"id":"https://openalex.org/S4306525896","display_name":"Research Square","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Research Square","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.researchsquare.com/article/rs-10713654/latest.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5147423714","display_name":"Konrad Barnowski","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I126596746","display_name":"Jagiellonian University","ror":"https://ror.org/03bqmcz70","country_code":"PL","type":"education","lineage":["https://openalex.org/I126596746"]}],"countries":["PL"],"is_corresponding":false,"raw_author_name":"Konrad Barnowski","raw_affiliation_strings":["Jagiellonian University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Jagiellonian University","institution_ids":["https://openalex.org/I126596746"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5029612146","display_name":"Marzena Lenart","orcid":"https://orcid.org/0000-0001-6176-2891","observed_orcids":["https://orcid.org/0000-0001-6176-2891"]},"institutions":[{"id":"https://openalex.org/I126596746","display_name":"Jagiellonian University","ror":"https://ror.org/03bqmcz70","country_code":"PL","type":"education","lineage":["https://openalex.org/I126596746"]}],"countries":["PL"],"is_corresponding":false,"raw_author_name":"Marzena Lenart","raw_affiliation_strings":["Jagiellonian University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Jagiellonian University","institution_ids":["https://openalex.org/I126596746"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5125387888","display_name":"Ping Lv","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I55712492","display_name":"Zhejiang University of Technology","ror":"https://ror.org/02djqfd08","country_code":"CN","type":"education","lineage":["https://openalex.org/I55712492"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Ping Lv","raw_affiliation_strings":["Zhejiang University of Technology"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Zhejiang University of Technology","institution_ids":["https://openalex.org/I55712492"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5109404733","display_name":"Sylwia W\u00f3jcik","orcid":"https://orcid.org/0000-0002-7477-0679","observed_orcids":["https://orcid.org/0000-0002-7477-0679"]},"institutions":[{"id":"https://openalex.org/I126596746","display_name":"Jagiellonian University","ror":"https://ror.org/03bqmcz70","country_code":"PL","type":"education","lineage":["https://openalex.org/I126596746"]}],"countries":["PL"],"is_corresponding":false,"raw_author_name":"Sylwia Wojcik","raw_affiliation_strings":["Jagiellonian University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Jagiellonian University","institution_ids":["https://openalex.org/I126596746"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5136711126","display_name":"Katarzyna Nakielska","orcid":"https://orcid.org/0009-0007-2993-5562","observed_orcids":["https://orcid.org/0009-0007-2993-5562"]},"institutions":[{"id":"https://openalex.org/I126596746","display_name":"Jagiellonian University","ror":"https://ror.org/03bqmcz70","country_code":"PL","type":"education","lineage":["https://openalex.org/I126596746"]}],"countries":["PL"],"is_corresponding":false,"raw_author_name":"Katarzyna Nakielska","raw_affiliation_strings":["Jagiellonian University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Jagiellonian University","institution_ids":["https://openalex.org/I126596746"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5002358496","display_name":"Justyna Kocik-Krol","orcid":"https://orcid.org/0000-0002-3779-3118","observed_orcids":["https://orcid.org/0000-0002-3779-3118"]},"institutions":[{"id":"https://openalex.org/I126596746","display_name":"Jagiellonian University","ror":"https://ror.org/03bqmcz70","country_code":"PL","type":"education","lineage":["https://openalex.org/I126596746"]}],"countries":["PL"],"is_corresponding":false,"raw_author_name":"Justyna Kocik-Krol","raw_affiliation_strings":["Jagiellonian University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Jagiellonian University","institution_ids":["https://openalex.org/I126596746"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5060145089","display_name":"Judyta Cielecka\u2010Piontek","orcid":"https://orcid.org/0000-0003-0891-5419","observed_orcids":["https://orcid.org/0000-0003-0891-5419"]},"institutions":[{"id":"https://openalex.org/I120230055","display_name":"Poznan University of Medical Sciences","ror":"https://ror.org/02zbb2597","country_code":"PL","type":"education","lineage":["https://openalex.org/I120230055"]}],"countries":["PL"],"is_corresponding":false,"raw_author_name":"Judyta Cielecka-Piontek","raw_affiliation_strings":["Poznan University of Medical Sciences"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Poznan University of Medical Sciences","institution_ids":["https://openalex.org/I120230055"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5070187736","display_name":"Anna Stasi\u0142owicz-Krzemie\u0144","orcid":"https://orcid.org/0000-0001-5211-661X","observed_orcids":["https://orcid.org/0000-0001-5211-661X"]},"institutions":[{"id":"https://openalex.org/I120230055","display_name":"Poznan University of Medical Sciences","ror":"https://ror.org/02zbb2597","country_code":"PL","type":"education","lineage":["https://openalex.org/I120230055"]}],"countries":["PL"],"is_corresponding":false,"raw_author_name":"Anna Stasi\u0142owicz-Krzemie\u0144","raw_affiliation_strings":["Poznan University of Medical Sciences"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Poznan University of Medical Sciences","institution_ids":["https://openalex.org/I120230055"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5114792652","display_name":"Riccardo Fusco","orcid":"https://orcid.org/0009-0002-7510-0770","observed_orcids":["https://orcid.org/0009-0002-7510-0770"]},"institutions":[{"id":"https://openalex.org/I70703428","display_name":"Palack\u00fd University Olomouc","ror":"https://ror.org/04qxnmv42","country_code":"CZ","type":"education","lineage":["https://openalex.org/I70703428"]}],"countries":["CZ"],"is_corresponding":false,"raw_author_name":"Fusco Riccardo","raw_affiliation_strings":["Palack\u00fd University Olomouc"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Palack\u00fd University Olomouc","institution_ids":["https://openalex.org/I70703428"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5147391766","display_name":"Alexander Doemling","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I70703428","display_name":"Palack\u00fd University Olomouc","ror":"https://ror.org/04qxnmv42","country_code":"CZ","type":"education","lineage":["https://openalex.org/I70703428"]}],"countries":["CZ"],"is_corresponding":false,"raw_author_name":"Alexander Doemling","raw_affiliation_strings":["Palack\u00fd University Olomouc"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Palack\u00fd University Olomouc","institution_ids":["https://openalex.org/I70703428"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5064915633","display_name":"Justyna Kalinowska\u2010T\u0142u\u015bcik","orcid":"https://orcid.org/0000-0001-7714-1651","observed_orcids":["https://orcid.org/0000-0001-7714-1651"]},"institutions":[{"id":"https://openalex.org/I126596746","display_name":"Jagiellonian University","ror":"https://ror.org/03bqmcz70","country_code":"PL","type":"education","lineage":["https://openalex.org/I126596746"]}],"countries":["PL"],"is_corresponding":false,"raw_author_name":"Justyna Kalinowska-T\u0142u\u015bcik","raw_affiliation_strings":["Jagiellonian University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Jagiellonian University","institution_ids":["https://openalex.org/I126596746"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5061498430","display_name":"Marta Karpiel","orcid":"https://orcid.org/0000-0001-9145-0186","observed_orcids":["https://orcid.org/0000-0001-9145-0186"]},"institutions":[{"id":"https://openalex.org/I126596746","display_name":"Jagiellonian University","ror":"https://ror.org/03bqmcz70","country_code":"PL","type":"education","lineage":["https://openalex.org/I126596746"]}],"countries":["PL"],"is_corresponding":false,"raw_author_name":"Marta Karpiel","raw_affiliation_strings":["Jagiellonian University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Jagiellonian University","institution_ids":["https://openalex.org/I126596746"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5081866399","display_name":"Szymon Buda","orcid":"https://orcid.org/0000-0003-3711-3570","observed_orcids":["https://orcid.org/0000-0003-3711-3570"]},"institutions":[{"id":"https://openalex.org/I126596746","display_name":"Jagiellonian University","ror":"https://ror.org/03bqmcz70","country_code":"PL","type":"education","lineage":["https://openalex.org/I126596746"]}],"countries":["PL"],"is_corresponding":false,"raw_author_name":"Szymon Buda","raw_affiliation_strings":["Jagiellonian University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Jagiellonian University","institution_ids":["https://openalex.org/I126596746"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5063454925","display_name":"Katarzyna Magiera\u2010Mularz","orcid":"https://orcid.org/0000-0002-4826-6380","observed_orcids":["https://orcid.org/0000-0002-4826-6380"]},"institutions":[{"id":"https://openalex.org/I126596746","display_name":"Jagiellonian University","ror":"https://ror.org/03bqmcz70","country_code":"PL","type":"education","lineage":["https://openalex.org/I126596746"]}],"countries":["PL"],"is_corresponding":false,"raw_author_name":"Katarzyna Magiera-Mularz","raw_affiliation_strings":["Jagiellonian University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Jagiellonian University","institution_ids":["https://openalex.org/I126596746"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5088542812","display_name":"Ewa Surmiak","orcid":"https://orcid.org/0000-0002-4103-4675","observed_orcids":["https://orcid.org/0000-0002-4103-4675"]},"institutions":[{"id":"https://openalex.org/I126596746","display_name":"Jagiellonian University","ror":"https://ror.org/03bqmcz70","country_code":"PL","type":"education","lineage":["https://openalex.org/I126596746"]}],"countries":["PL"],"is_corresponding":false,"raw_author_name":"Ewa Surmiak","raw_affiliation_strings":["Jagiellonian University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Jagiellonian University","institution_ids":["https://openalex.org/I126596746"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5014775737","display_name":"Bogdan Musielak","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I126596746","display_name":"Jagiellonian University","ror":"https://ror.org/03bqmcz70","country_code":"PL","type":"education","lineage":["https://openalex.org/I126596746"]}],"countries":["PL"],"is_corresponding":false,"raw_author_name":"Bogdan Musielak","raw_affiliation_strings":["Jagiellonian University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Jagiellonian University","institution_ids":["https://openalex.org/I126596746"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5001108606","display_name":"Maciej Siedlar","orcid":"https://orcid.org/0000-0002-3904-5412","observed_orcids":["https://orcid.org/0000-0002-3904-5412","https://orcid.org/0000-0003-0540-5659"]},"institutions":[{"id":"https://openalex.org/I126596746","display_name":"Jagiellonian University","ror":"https://ror.org/03bqmcz70","country_code":"PL","type":"education","lineage":["https://openalex.org/I126596746"]}],"countries":["PL"],"is_corresponding":false,"raw_author_name":"Maciej Siedlar","raw_affiliation_strings":["Jagiellonian University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Jagiellonian University","institution_ids":["https://openalex.org/I126596746"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5082119450","display_name":"Bo\u017cena Skupie\u0144-Rabian","orcid":"https://orcid.org/0000-0002-1131-2582","observed_orcids":["https://orcid.org/0000-0002-1131-2582"]},"institutions":[{"id":"https://openalex.org/I126596746","display_name":"Jagiellonian University","ror":"https://ror.org/03bqmcz70","country_code":"PL","type":"education","lineage":["https://openalex.org/I126596746"]}],"countries":["PL"],"is_corresponding":false,"raw_author_name":"Bozena Skupien-Rabian","raw_affiliation_strings":["Jagiellonian University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Jagiellonian University","institution_ids":["https://openalex.org/I126596746"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5077187677","display_name":"Urszula Jankowska","orcid":"https://orcid.org/0000-0002-7165-8964","observed_orcids":["https://orcid.org/0000-0002-7165-8964"]},"institutions":[{"id":"https://openalex.org/I126596746","display_name":"Jagiellonian University","ror":"https://ror.org/03bqmcz70","country_code":"PL","type":"education","lineage":["https://openalex.org/I126596746"]}],"countries":["PL"],"is_corresponding":false,"raw_author_name":"Urszula Jankowska","raw_affiliation_strings":["Jagiellonian University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Jagiellonian University","institution_ids":["https://openalex.org/I126596746"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5147414945","display_name":"Wen Zhang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I55712492","display_name":"Zhejiang University of Technology","ror":"https://ror.org/02djqfd08","country_code":"CN","type":"education","lineage":["https://openalex.org/I55712492"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Wen Zhang","raw_affiliation_strings":["Zhejiang University of Technology"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Zhejiang University of Technology","institution_ids":["https://openalex.org/I55712492"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5033794082","display_name":"Jacek Plewka","orcid":"https://orcid.org/0000-0002-0307-0907","observed_orcids":["https://orcid.org/0000-0002-0307-0907"]},"institutions":[{"id":"https://openalex.org/I126596746","display_name":"Jagiellonian University","ror":"https://ror.org/03bqmcz70","country_code":"PL","type":"education","lineage":["https://openalex.org/I126596746"]}],"countries":["PL"],"is_corresponding":false,"raw_author_name":"Jacek Plewka","raw_affiliation_strings":["Jagiellonian University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Jagiellonian University","institution_ids":["https://openalex.org/I126596746"]}]}],"institutions":[],"countries_distinct_count":3,"institutions_distinct_count":4,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.9965999722480774,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.9965999722480774,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T12582","display_name":"Flavonoids in Medical Research","score":0.00139999995008111,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10580","display_name":"Immunotherapy and Immune Responses","score":0.000699999975040555,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/apigenin","display_name":"apigenin","score":0.9990000128746033},{"id":"https://openalex.org/keywords/lag-3","display_name":"LAG-3","score":0.9869999885559082},{"id":"https://openalex.org/keywords/small-molecule-inhibitors","display_name":"small molecule inhibitors","score":0.7979999780654907},{"id":"https://openalex.org/keywords/pd-l1-blockade","display_name":"PD-L1 blockade","score":0.9470000267028809},{"id":"https://openalex.org/keywords/durvalumab","display_name":"durvalumab","score":0.781000018119812},{"id":"https://openalex.org/keywords/immune-checkpoint-blockade","display_name":"immune checkpoint blockade","score":0.7089999914169312},{"id":"https://openalex.org/keywords/flavonoids","display_name":"flavonoids","score":0.6349999904632568},{"id":"https://openalex.org/keywords/t-cell-activation","display_name":"T cell activation","score":0.7110000252723694},{"id":"https://openalex.org/keywords/combination-immunotherapy","display_name":"combination immunotherapy","score":0.7289999723434448},{"id":"https://openalex.org/keywords/synergistic-effect","display_name":"synergistic effect","score":0.4000000059604645},{"id":"https://openalex.org/keywords/immune-exclusion","display_name":"immune exclusion","score":0.5799999833106995},{"id":"https://openalex.org/keywords/cd8-t-cells","display_name":"CD8+ T cells","score":0.7390000224113464},{"id":"https://openalex.org/keywords/antitumor-immunity","display_name":"antitumor immunity","score":0.7329999804496765},{"id":"https://openalex.org/keywords/mc38-tumor-model","display_name":"MC38 tumor","score":0.7310000061988831},{"id":"https://openalex.org/keywords/cd69","display_name":"CD69","score":0.4390000104904175}],"concepts":[{"id":"https://openalex.org/C2778609962","wikidata":"https://www.wikidata.org/wiki/Q424567","display_name":"Apigenin","level":4,"score":0.8489999771118164},{"id":"https://openalex.org/C2777742743","wikidata":"https://www.wikidata.org/wiki/Q19904005","display_name":"Durvalumab","level":5,"score":0.6136999726295471},{"id":"https://openalex.org/C2778468042","wikidata":"https://www.wikidata.org/wiki/Q273976","display_name":"Blockade","level":3,"score":0.5925999879837036},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5871000289916992},{"id":"https://openalex.org/C2780674031","wikidata":"https://www.wikidata.org/wiki/Q2012719","display_name":"Cancer immunotherapy","level":4,"score":0.5497999787330627},{"id":"https://openalex.org/C2780851360","wikidata":"https://www.wikidata.org/wiki/Q21686041","display_name":"Immune checkpoint","level":4,"score":0.4726000130176544},{"id":"https://openalex.org/C179464577","wikidata":"https://www.wikidata.org/wiki/Q1632589","display_name":"Jurkat cells","level":4,"score":0.44830000400543213},{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.4388999938964844},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4318999946117401},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.42410001158714294},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.41510000824928284},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.35429999232292175},{"id":"https://openalex.org/C25824698","wikidata":"https://www.wikidata.org/wiki/Q6840012","display_name":"Microscale thermophoresis","level":2,"score":0.3499999940395355},{"id":"https://openalex.org/C2777252647","wikidata":"https://www.wikidata.org/wiki/Q411310","display_name":"Hesperetin","level":4,"score":0.3416999876499176},{"id":"https://openalex.org/C2776999253","wikidata":"https://www.wikidata.org/wiki/Q1304270","display_name":"Combination therapy","level":2,"score":0.3310000002384186},{"id":"https://openalex.org/C159654299","wikidata":"https://www.wikidata.org/wiki/Q79460","display_name":"Antibody","level":2,"score":0.32600000500679016},{"id":"https://openalex.org/C542903549","wikidata":"https://www.wikidata.org/wiki/Q422248","display_name":"Monoclonal antibody","level":3,"score":0.31220000982284546},{"id":"https://openalex.org/C77255625","wikidata":"https://www.wikidata.org/wiki/Q402093","display_name":"Reprogramming","level":3,"score":0.3077000081539154},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.3027999997138977},{"id":"https://openalex.org/C195616568","wikidata":"https://www.wikidata.org/wiki/Q128711","display_name":"Epitope","level":3,"score":0.30070000886917114},{"id":"https://openalex.org/C2777658100","wikidata":"https://www.wikidata.org/wiki/Q180614","display_name":"Melanoma","level":2,"score":0.289900004863739},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.28760001063346863},{"id":"https://openalex.org/C96232424","wikidata":"https://www.wikidata.org/wiki/Q4118072","display_name":"Cancer cell","level":3,"score":0.2827000021934509},{"id":"https://openalex.org/C2780914512","wikidata":"https://www.wikidata.org/wiki/Q25323943","display_name":"H3K4me3","level":5,"score":0.27950000762939453},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.27720001339912415},{"id":"https://openalex.org/C553184892","wikidata":"https://www.wikidata.org/wiki/Q1141429","display_name":"Flow cytometry","level":2,"score":0.26269999146461487},{"id":"https://openalex.org/C2778650287","wikidata":"https://www.wikidata.org/wiki/Q7838098","display_name":"Tremelimumab","level":5,"score":0.2574999928474426},{"id":"https://openalex.org/C40677261","wikidata":"https://www.wikidata.org/wiki/Q21418091","display_name":"Antibody-dependent cell-mediated cytotoxicity","level":4,"score":0.2513999938964844}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.21203/rs.3.rs-10713654/v1","doi":"https://doi.org/10.21203/rs.3.rs-10713654/v1","is_oa":true,"landing_page_url":"https://doi.org/10.21203/rs.3.rs-10713654/v1","pdf_url":"https://www.researchsquare.com/article/rs-10713654/latest.pdf","source":{"id":"https://openalex.org/S4306525896","display_name":"Research Square","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Research Square","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.21203/rs.3.rs-10713654/v1","doi":"https://doi.org/10.21203/rs.3.rs-10713654/v1","is_oa":true,"landing_page_url":"https://doi.org/10.21203/rs.3.rs-10713654/v1","pdf_url":"https://www.researchsquare.com/article/rs-10713654/latest.pdf","source":{"id":"https://openalex.org/S4306525896","display_name":"Research Square","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Research Square","raw_type":"posted-content"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.9940000176429749,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G174677250","display_name":null,"funder_award_id":"POIR.04.02.00-00-D001/20","funder_id":"https://openalex.org/F4320321001","funder_display_name":"National Natural Science Foundation of China"},{"id":"https://openalex.org/G2007373855","display_name":null,"funder_award_id":"22177105","funder_id":"https://openalex.org/F4320321001","funder_display_name":"National Natural Science Foundation of China"},{"id":"https://openalex.org/G4622733388","display_name":null,"funder_award_id":"04.02.00-00-D001/20","funder_id":"https://openalex.org/F4320320300","funder_display_name":"European Commission"},{"id":"https://openalex.org/G5436491568","display_name":null,"funder_award_id":"POIR.04.02","funder_id":"https://openalex.org/F4320320300","funder_display_name":"European Commission"},{"id":"https://openalex.org/G594687368","display_name":null,"funder_award_id":"POIR.04.02.00-00-D001/20","funder_id":"https://openalex.org/F4320322650","funder_display_name":"Narodowym Centrum Nauki"},{"id":"https://openalex.org/G649876508","display_name":null,"funder_award_id":"POIR.04.02.00\u201000\u2010D001/20","funder_id":"https://openalex.org/F4320320300","funder_display_name":"European Commission"}],"funders":[{"id":"https://openalex.org/F4320320300","display_name":"European Commission","ror":"https://ror.org/00k4n6c32"},{"id":"https://openalex.org/F4320321001","display_name":"National Natural Science Foundation of China","ror":"https://ror.org/01h0zpd94"},{"id":"https://openalex.org/F4320322650","display_name":"Narodowym Centrum Nauki","ror":"https://ror.org/03ha2q922"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7203675740.pdf","grobid_xml":"https://content.openalex.org/works/W7203675740.grobid-xml"},"referenced_works_count":40,"referenced_works":["https://openalex.org/W1031578623","https://openalex.org/W1988437166","https://openalex.org/W1992249154","https://openalex.org/W2036321220","https://openalex.org/W2039123767","https://openalex.org/W2041599929","https://openalex.org/W2052030759","https://openalex.org/W2060079863","https://openalex.org/W2068487611","https://openalex.org/W2070753604","https://openalex.org/W2107556275","https://openalex.org/W2466059604","https://openalex.org/W2544360569","https://openalex.org/W2765596630","https://openalex.org/W2789936040","https://openalex.org/W2791483720","https://openalex.org/W2808421749","https://openalex.org/W2890051541","https://openalex.org/W2898843431","https://openalex.org/W2906369032","https://openalex.org/W2921026906","https://openalex.org/W2942213745","https://openalex.org/W2991106430","https://openalex.org/W3084051281","https://openalex.org/W3087624166","https://openalex.org/W3169596185","https://openalex.org/W3195008613","https://openalex.org/W4206239577","https://openalex.org/W4223627273","https://openalex.org/W4385295693","https://openalex.org/W4391375908","https://openalex.org/W4392796921","https://openalex.org/W4400672265","https://openalex.org/W4400965455","https://openalex.org/W4405476449","https://openalex.org/W4409168037","https://openalex.org/W4410757946","https://openalex.org/W4411140362","https://openalex.org/W4412751613","https://openalex.org/W4413412127"],"related_works":["https://openalex.org/W4280498477","https://openalex.org/W3120367533","https://openalex.org/W4364363213","https://openalex.org/W7154498494","https://openalex.org/W4409696621","https://openalex.org/W4223917942","https://openalex.org/W3083106776","https://openalex.org/W4414555444","https://openalex.org/W4415589543","https://openalex.org/W2966923691"],"abstract_inverted_index":{"Abstract":[0],"Background":[1],"Immune":[2],"checkpoint":[3,33,323],"blockade":[4,23,289],"targeting":[5],"PD-1/PD-L1":[6],"and":[7,21,43,66,103,108,122,140,163,180,211,214,231,234,238,261,265,285,314],"LAG-3":[8,20,50,166,279],"has":[9],"demonstrated":[10],"significant":[11],"clinical":[12,29],"benefit.":[13],"The":[14],"recent":[15],"FDA":[16],"approval":[17],"of":[18,31,46,49,87,94,224,229,236,278],"combined":[19],"PD-1":[22],"(relatlimab":[24],"plus":[25],"nivolumab)":[26],"shows":[27],"the":[28,44,88,112,160,207,255,282],"value":[30],"dual":[32,322],"inhibition.":[34],"Current":[35],"strategies":[36],"rely":[37],"almost":[38],"exclusively":[39],"on":[40],"monoclonal":[41],"antibodies,":[42],"development":[45],"small-molecule":[47,73,276],"modulators":[48],"remains":[51],"largely":[52],"unexplored.":[53],"Here,":[54],"we":[55],"investigate":[56],"whether":[57],"apigenin,":[58],"a":[59,72,149,196,221,274,311,319],"naturally":[60],"occurring":[61],"flavonoid":[62],"with":[63,111,125,183,227,242,287],"reported":[64],"anticancer":[65],"immunomodulatory":[67],"properties,":[68],"can":[69,307],"serve":[70],"as":[71,318],"alternative":[74],"to":[75,137,290],"anti-LAG-3":[76],"antibodies":[77],"in":[78,118,148,167],"combination":[79,109,208,247],"immunotherapy.":[80,324],"Methods":[81],"Flavonoids":[82],"were":[83,116],"screened":[84],"for":[85,321],"disruption":[86],"LAG-3/MHCII":[89,161,283],"interaction":[90,162],"using":[91,128],"HTRF.":[92],"Binding":[93],"apigenin":[95,176],"was":[96,135,146],"validated":[97],"by":[98,201,305,310],"molecular":[99],"dynamics,":[100],"microscale":[101],"thermophoresis":[102],"chemoproteomic":[104],"pull-down.":[105],"Functional":[106],"activity":[107,171],"effects":[110],"anti-PD-L1":[113],"antibody":[114],"durvalumab":[115],"assessed":[117],"Jurkat":[119],"reporter":[120],"assays":[121],"human":[123,155,205],"PBMCs,":[124,206],"synergy":[126],"quantified":[127],"Bliss":[129],"independence":[130],"modeling.":[131],"A":[132],"polymeric":[133],"formulation":[134],"developed":[136],"improve":[138],"solubility":[139],"reduce":[141],"nonspecific":[142],"cytotoxicity.":[143],"Antitumor":[144],"efficacy":[145],"evaluated":[147],"syngeneic":[150],"MC38":[151],"mice":[152],"model":[153],"expressing":[154],"PD-L1.":[156],"Results":[157],"Apigenin":[158,272],"disrupted":[159],"directly":[164],"bound":[165],"cells,":[168],"without":[169,268],"detectable":[170,269],"against":[172],"PD-1/PD-L1.":[173],"Functionally,":[174],"formulated":[175],"restored":[177],"T-cell":[178,225,259],"activation":[179],"worked":[181],"synergistically":[182],"durvalumab,":[184],"yielding":[185],"uniformly":[186],"positive":[187],"Bliss-independence":[188],"scores":[189],"(peaking":[190],"at":[191],"\u0394Bliss":[192],"\u2248":[193],"0.20)":[194],"within":[195],"non-toxic":[197],"concentration":[198],"range":[199],"enabled":[200],"formulation.":[202],"In":[203,245],"primary":[204],"increased":[209,254],"CD69":[210],"CD137":[212],"expression":[213,267],"raised":[215,262],"IFN-\u03b3":[216],"production.":[217],"Quantitative":[218],"proteomics":[219],"showed":[220],"coordinated":[222],"reprogramming":[223],"programs,":[226],"up-regulation":[228],"immune-activation":[230],"leukocyte-migration":[232],"pathways":[233],"down-regulation":[235],"extracellular-matrix":[237],"tissue-remodeling":[239],"programs":[240],"associated":[241],"immune":[243,300],"exclusion.":[244],"vivo,":[246],"therapy":[248],"significantly":[249],"improved":[250],"tumor":[251],"growth":[252],"inhibition,":[253],"intratumoral":[256],"CD8":[257],"+":[258],"frequency,":[260],"granzyme":[263],"B":[264],"perforin":[266],"toxicity.":[270],"Conclusions":[271],"is":[273],"direct":[275],"inhibitor":[277],"that":[280,297],"disrupts":[281],"interface":[284],"synergizes":[286],"PD-L1":[288],"increase":[291],"antitumor":[292],"immunity.":[293],"These":[294],"findings":[295],"show":[296],"an":[298],"inhibitory":[299],"receptor":[301],"traditionally":[302],"addressed":[303],"only":[304],"biologics":[306],"be":[308],"engaged":[309],"small":[312],"molecule,":[313],"support":[315],"antibody\u2013small-molecule":[316],"combinations":[317],"strategy":[320]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-08-19T00:00:00"}
