{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:11:01Z","timestamp":1788919861067,"version":"build-2803163510"},"reference-count":136,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Three-dimensional tumor organoids, particularly patient-derived organoids (PDOs), recapitulate key morphological, genetic, and functional features of original tumors. Co-culture with immune cells enables studies of the tumor immune microenvironment (TIME) and holds promise for personalized immunotherapy. In this review, we critically evaluate established methodologies for tumor organoid-immune cell co-culture, including reductionist, holistic (tumor slice culture and air-liquid interface), and organoid-on-a-chip approaches. We provide quantitative benchmarking of success rates, immune cell persistence, and predictive accuracy, and discuss contradictory findings, reproducibility challenges, and technical barriers that limit clinical translation. We also analyze how these systems reveal mechanisms of antitumor immunity and immune escape, and assess their applications in immune checkpoint blockade screening, adoptive cell therapy (CAR-T, CAR-NK, \u03b3\u03b4 T cells), and emerging \u201corganoid+\u201d technologies including spatial transcriptomics, AI-assisted imaging, and machine learning. Finally, we address ethical, regulatory, and standardization issues. Despite substantial progress, current systems face major limitations\u2014including batch variability, loss of native heterogeneity, insufficient vascularization, and lack of systemic immune modeling\u2014that must be overcome before clinical adoption.<\/jats:p>","DOI":"10.3389\/fcell.2026.1865487","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:40:35Z","timestamp":1784785235000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Tumor organoid-immune cell co-culture systems for precision oncology"],"prefix":"10.3389","volume":"14","author":[{"given":"Lei","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Breast Surgery, The Fourth Affiliated Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfeng","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Mianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feihong","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongke","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology, Dianjiang People\u2019s Hospital of Chongqing","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.3390\/vaccines9111363","article-title":"The advantages and challenges of anticancer dendritic cell vaccines and NK cells in adoptive cell immunotherapy","volume":"9","author":"Abakushina","year":"2021","journal-title":"Vaccines (Basel)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1093\/neuonc\/noab273","article-title":"Establishment of patient-derived organoid models of lower-grade glioma","volume":"24","author":"Abdullah","year":"2022","journal-title":"Neuro-oncology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/978-981-15-3266-5_3","article-title":"Roles of PD-1\/PD-L1 pathway: Signaling, cancer, and beyond","volume":"1248","author":"Ai","year":"2020","journal-title":"Adv. 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