{"doi":"10.1016/j.mtbio.2025.101925","title":"A microfluidic tumor-on-chip platform deciphers hypoxia-driven FOXO3a/PD-L1 signaling in gastric cancer immunotherapy resistance","abstract":null,"journal":"Materials Today Bio","year":2025,"id":639971,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":693843,"name":"Fangqian Chen","orcid":"0000-0003-4570-0089","position":1,"is_corresponding":false},{"id":1663099,"name":"Zhebin Dong","orcid":null,"position":2,"is_corresponding":false},{"id":1663100,"name":"Xianlei Cai","orcid":null,"position":3,"is_corresponding":false},{"id":820551,"name":"Yuan Xu","orcid":"0000-0002-3694-2871","position":4,"is_corresponding":false},{"id":824882,"name":"Zhengwei Chen","orcid":"0000-0003-3067-0155","position":5,"is_corresponding":false},{"id":1663101,"name":"Sangsang Chen","orcid":null,"position":6,"is_corresponding":false},{"id":1663102,"name":"Tianci Chen","orcid":null,"position":7,"is_corresponding":false},{"id":1663103,"name":"Jiarong Huang","orcid":null,"position":8,"is_corresponding":false},{"id":32625,"name":"Fangfang Chen","orcid":"0000-0002-0854-1667","position":9,"is_corresponding":false},{"id":1663104,"name":"Yahua Zheng","orcid":null,"position":10,"is_corresponding":false},{"id":936879,"name":"Jingyun Ma","orcid":"0000-0001-6285-312X","position":11,"is_corresponding":false},{"id":534722,"name":"Weiming Yu","orcid":"0000-0002-8408-2888","position":12,"is_corresponding":false},{"id":659630,"name":"Chao Liang","orcid":"0000-0002-0414-690X","position":13,"is_corresponding":false},{"id":1663098,"name":"Hanting Xiang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A microfluidic tumor-on-chip platform deciphers hypoxia-driven FOXO3a/PD-L1 signaling in gastric cancer immunotherapy resistance","abstract":"Hypoxia represents a common feature within the microenvironment of various cancerous tumors, which suppresses tumor immunogenicity. Immunotherapy, particularly based on immune checkpoint inhibitors, significantly alters the prognosis of certain tumors and reveals the presence of intrinsic or acquired resistance. Presently available platforms, however, cannot efficiently recapitulate the in vivo tumor microenvironment and elucidate the mechanisms of hypoxia-induced immunotherapy resistance in tumors. In this study, a microfluidic tumor-on-chip model is employed to investigate immunotherapy resistance in gastric cancer (GC) cells within a hypoxic microenvironment. Unlike traditional methods, this chip accurately and efficiently replicates the in vivo tumor hypoxic microenvironment. This microfluidic platform demonstrates the upregulation of the forkhead box O3 (FOXO3a) under hypoxic conditions, subsequently activating downstream programmed cell death ligand-1 (PD-L1) expression, ultimately leading to immunotherapy resistance. In a syngeneic mouse model, FOXO3a deficiency restores sensitivity to immunotherapy by enhancing immune cell enrichment. In clinical samples, FOXO3a levels and the prognosis of patients with gastric cancer receiving immunotherapy are correlated. In summary, by constructing a novel microfluidic chip, the in vivo tumor microenvironment can be efficiently simulated, uncovering the pivotal role of FOXO3a in immunotherapy resistance in gastric cancer.","is_dataset_classified":null,"base_score":2.302585092994046,"endowment":2.302585092994046,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40534828","pmcid":"PMC12173698","openalex_id":"https://openalex.org/W4410973507","authors":[],"funders":[{"funder_name":"Zhejiang Province Natural Science Foundation","grant_id":"LBY24H200001","title":null},{"funder_name":"Zhejiang Province Natural Science Foundation","grant_id":"LTGY24B050001","title":null},{"funder_name":"Medical Science and Technology Project of Zhejiang Province","grant_id":"2023KY1033","title":null},{"funder_name":"Medical Science and Technology Project of Zhejiang Province","grant_id":"2023KY236","title":null},{"funder_name":"Medical Science and Technology Project of Zhejiang Province","grant_id":"2022KY1091","title":null},{"funder_name":"Ningbo Municipal Natural Science Foundation","grant_id":"2022J264","title":null},{"funder_name":"Ningbo Municipal Natural Science Foundation","grant_id":"2022J252","title":null},{"funder_name":"Ningbo Municipal Natural Science Foundation","grant_id":"2021J279","title":null},{"funder_name":"Zhejiang Provincial Ten Thousand Plan for Young Top Talents","grant_id":"","title":null}],"total_grants":9,"fwci":3.7957,"citation_percentile":0.93905518,"influential_citations":0,"citation_trend":[{"year":2025,"count":1},{"year":2026,"count":8}],"oa_status":"gold","license":"cc-by-nc-nd","oa_locations":[{"url":"https://doi.org/10.1016/j.mtbio.2025.101925","host_type":"journal"},{"url":"https://doi.org/10.1016/j.mtbio.2025.101925","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2590006425004958?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2590006425004958?httpAccept=text/plain","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40534828","host_type":"repository"},{"url":"https://doaj.org/article/922b29c01cf943759e84285193a42f86","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12173698","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12173698","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12173698?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["FOXO transcription factor regulation","Cancer Immunotherapy and Biomarkers","Cancer-related molecular mechanisms research"],"mesh_terms":[],"keywords":["Immunotherapy","Tumor microenvironment","Cancer research","Cancer immunotherapy","Immune system","Cancer","Downregulation and upregulation","In vivo","Immunogenicity","Biology","Medicine","Immunology","Internal medicine","Hypoxia","Gastric cancer","Foxo3a","microfluidic chip","Immunotherapy Resistance"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-07T05:16:01.526094Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}