{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T02:01:57Z","timestamp":1782525717404,"version":"3.54.5"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Pancreatic cancer is notably resistant to treatment, primarily due to its dense desmoplastic stroma and immunosuppressive microenvironment. Accurately modeling this complex landscape and its immunosuppressive hallmarks in vitro is highly valuable for screening immunotherapeutic strategies. However, replicating these intricate features remains a significant challenge. Herein, we bioengineered miniaturized tumor\u2010stroma platforms that combine cancer and stromal cells, as well as extracellular matrix mimetic biomaterials as a strategy to emulate the native tumor composition and key tumor immunosuppressive signatures. Bioengineered stratified tumor\u2010stroma pancreatic cancer models, so termed cancer\u2010on\u2010a\u2010bead platforms are generated in superhydrophobic surfaces and co\u2010cultured with T cells, dendritic cells, as well as M0 macrophages, as a strategy to recapitulate tumor\u2010immune interplay. The generated models revealed suppression of antigen presentation, M2 macrophage polarization, and T cell exhaustion, representing key features of this neoplasia. The screening of antibody mediated immunotherapy in the 3D tumor platforms, using clinically approved anti PD\u20101 antibody as a model therapeutic, partially restored T cell function. Overall, our findings demonstrate compartmentalized tumor\u2010stroma models potential for being used to screen candidate immunotherapeutics for pancreatic cancer in a preclinical setting.<\/jats:p>","DOI":"10.1002\/adhm.202502758","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T11:34:39Z","timestamp":1764329679000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Bioengineered Pancreatic Cancer Immunosuppressive Microenvironment Models for Screening Immunotherapies"],"prefix":"10.1002","volume":"15","author":[{"given":"Maria V.","family":"Monteiro","sequence":"first","affiliation":[{"name":"Department of Chemistry CICECO \u2013 Aveiro Institute of Materials University of Aveiro Campus Universit\u00e1rio de Santiago  Aveiro Portugal"},{"name":"Cellularis Biomodels Pci Creative Science Park Aveiro Region Via do Conhecimento Edif\u00edcio Central  \u00cdlhavo Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarida","family":"Henriques\u2010Pereira","sequence":"additional","affiliation":[{"name":"Department of Chemistry CICECO \u2013 Aveiro Institute of Materials University of Aveiro Campus Universit\u00e1rio de Santiago  Aveiro Portugal"},{"name":"Cellularis Biomodels Pci Creative Science Park Aveiro Region Via do Conhecimento Edif\u00edcio Central  \u00cdlhavo Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno M.","family":"Neves","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Institute of Biomedicine \u2013 iBiMED University of Aveiro  Aveiro Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0372-2493","authenticated-orcid":false,"given":"V\u00edtor M.","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Department of Chemistry CICECO \u2013 Aveiro Institute of Materials University of Aveiro Campus Universit\u00e1rio de Santiago  Aveiro Portugal"},{"name":"Cellularis Biomodels Pci Creative Science Park Aveiro Region Via do Conhecimento Edif\u00edcio Central  \u00cdlhavo Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2342-3765","authenticated-orcid":false,"given":"Jo\u00e3o F.","family":"Mano","sequence":"additional","affiliation":[{"name":"Department of Chemistry CICECO \u2013 Aveiro Institute of Materials University of Aveiro Campus Universit\u00e1rio de Santiago  Aveiro Portugal"},{"name":"Cellularis Biomodels Pci Creative Science Park Aveiro Region Via do Conhecimento Edif\u00edcio Central  \u00cdlhavo Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-022-00349-2"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16081470"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121653"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05351-1"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-024-00681-z"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-022-00741-1"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-023-02935-3"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14040995"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1113378"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24108707"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-018-0815-z"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-017-0448-5"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.26546"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14163994"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2024.06.008"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.4c01816"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/smtd.202001207"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202102574"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.4c11188"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40169-019-0226-9"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-019-0765-y"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2016.11.072"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-0677"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-0525"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0870"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)00078-4"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-0416"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.576399"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2023.189065"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11050721"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.62645"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-025-07164-0"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-025-01717-y"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01514"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0058-7"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2016.217"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2019.152691"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-018-0585-0"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00274"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2001-11-0017"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.181.2.775"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.05.011"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.10561"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22136995"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116930"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(94)90193-7"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.04.014"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00456-10"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.162"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-12-195792"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202305473"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202502758","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adhm.202502758","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202502758","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T20:03:01Z","timestamp":1773000181000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202502758"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,28]]},"references-count":51,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/adhm.202502758"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202502758","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,28]]},"assertion":[{"value":"2025-06-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02758"}}