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Our perfusion culture method extends tumor slice viability, maintaining stable tumor content, metabolism, stromal composition, and immune cell populations for 12 days. Using multiplexed immunofluorescence and spatial transcriptomics, we identify immune neighborhoods and potential for immunotherapy. We used avatars to assess the impact of a preclinically validated metabolic therapy and show recovery of stromal and immune phenotypes and tumor redifferentiation. To determine clinical relevance, we monitored avatar response to gemcitabine treatment and identify a patient avatar-predictable response from clinical follow-up. Thus, avatars provide valuable information for syngeneic testing of therapeutics and a truly personalized therapeutic assessment platform for patients.<\/jats:p>","DOI":"10.1126\/sciadv.adm9071","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T17:59:36Z","timestamp":1720202376000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":13,"title":["Development of human pancreatic cancer avatars as a model for dynamic immune landscape profiling and personalized therapy"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7167-1325","authenticated-orcid":true,"given":"Daniel","family":"Hughes","sequence":"first","affiliation":[{"name":"Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4793-1967","authenticated-orcid":true,"given":"Simei","family":"Go","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Eyres","sequence":"additional","affiliation":[{"name":"Medicines Discovery Catapult, Alderley Park SK10 4ZF, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuliu","family":"Pan","sequence":"additional","affiliation":[{"name":"NanoString Technologies Inc., Seattle, WA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somnath","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4213-4723","authenticated-orcid":true,"given":"Zahir","family":"Soonawalla","sequence":"additional","affiliation":[{"name":"Department of HPB surgery, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7DQ, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6038-944X","authenticated-orcid":true,"given":"Frances","family":"Willenbrock","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0060-6278","authenticated-orcid":true,"given":"Eric","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18071338"},{"key":"e_1_3_2_3_2","unstructured":"American Cancer Society Cancer Facts & Figures 2023 (American Cancer Society 2022); https:\/\/cancer.org\/research\/cancer-facts-statistics\/all-cancer-facts-figures\/2023-cancer-facts-figures.html."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21654"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12041024"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13014-019-1345-6"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2022.03.021"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2023.03.002"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-2972"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.171"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay2574"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109429"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.11.021"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-65911-3"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-81299-0"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.009"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/adbi.201800300"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10090316"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.974087"},{"key":"e_1_3_2_20_2","unstructured":"J. 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