{"doi":"10.1101/2022.09.09.507299","title":"An Immune Cell Recirculation-Enabled Microfluidic Array to Study Dynamic Immunotherapeutic Activity in Recapitulated Tumor Microenvironment","abstract":"ABSTRACT The efficacy of immunotherapeutic treatment protocols to enable immune cell mediated treatment of cancer is significantly modulated in the presence of tumor microenvironment (TME) which is a key factor in providing both a physical barrier and immunosuppressive stimuli. Herein, we developed a recirculating, high-throughput microfluidic cell array to capture these crucial players – cytotoxic T cells in circulation, endothelium, and tumor stroma. The system consisted of a three-layered cell array spatially emulating TME, with T cell circulation sustained via fluidic recirculating circuits. This allowed us to study the dynamic TME/circulation system and cancer cell response thereof. The system further revealed that tumor endothelium exhibited a hindrance to T cell infiltration into the breast cancer tumor compartment, which was alleviated when treated with anti-human PD-L1 antibody. The other key stromal component, cancer associated fibroblasts, further attenuated T cell infiltration, and led to reduced apoptosis activity in cancer cells. These results confirm the capability of our tumor-on-a-chip system to recapitulate some key immune cell interactions with the reconstructed TME, along with demon-strating as the feasibility of using this system for high-throughput cancer immunotherapeutic screening.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":311399,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":249850,"name":"Yeh‐Hsing Lao","orcid":"0000-0002-7990-199X","position":1,"is_corresponding":false},{"id":350489,"name":"A. H. Rezwanuddin Ahmed","orcid":"0000-0002-6073-5741","position":2,"is_corresponding":false},{"id":1007620,"name":"Siyu He","orcid":"0009-0007-5788-3595","position":3,"is_corresponding":false},{"id":109855,"name":"Taha Merghoub","orcid":"0000-0002-1518-5111","position":4,"is_corresponding":false},{"id":235103,"name":"Kam W. Leong","orcid":"0000-0002-8133-4955","position":5,"is_corresponding":false},{"id":1007621,"name":"Sihong Wang","orcid":"0000-0002-3611-0004","position":6,"is_corresponding":false},{"id":249853,"name":"Chun‐Wei Chi","orcid":"0000-0001-8068-6716","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T00:33:28.480200Z","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":[]}