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REVIEW article

Front. Cell Dev. Biol.

Sec. Cancer Cell Biology

Patient-Derived Organoids (PDOs): A Novel Preclinical Platform to Overcome Challenges in Cancer Immunotherapy

  • 1. Shanghai 411 Hospital, Shanghai, China

  • 2. Changhai Hospital, Shanghai, China

  • 3. Shanghai OneTar Biomedicine, shanghai, China

  • 4. Jiaxing University, Jiaxing, China

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Abstract

Cancer immunotherapy has revolutionized oncology but faces significant challenges including low response rates and lack of effective preclinical models. This review elucidates how patient-derived organoids (PDOs) are emerging as a transformative platform to address these hurdles. We detail sophisticated immuno-PDO (iPDO) models, categorized into reconstituted systems (co-culturing PDOs with exogenous immune cells) and native systems (preserving endogenous tumor microenvironment via Air-Liquid Interface or Patient-Derived Organotypic Tumor Spheroids). A problem-solution framework demonstrates how iPDOs: (1) deconvolute the immunosuppressive TME; (2) function as "living biomarkers" for predicting clinical responses; (3) unravel resistance mechanisms via multi-omics; and (4) empower high-throughput screening for personalized combination therapies. Integration with bioengineering, multi-omics, and AI heralds a new era in precision immuno-oncology, holding immense promise for deciphering resistance and improving clinical outcomes.

Summary

Keywords

biomarker, cancer immunotherapy, Immune checkpoint inhibitors (ICIs), patient-derived organoids (PDOs), Tumor microenvironment (TME)

Received

30 November 2025

Accepted

19 January 2026

Copyright

© 2026 Yin, Ni, Xing, Niu, Qiu, Wei, Luo and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Xiaolan Yin; Gang Chen

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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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