Fabiana Moresi, Francesco Noto, Jyothsna Vasudevan, Xavier Bisteau, Giulia Adriani, Andrea Pavesi
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Importantly, it is highlighted how these components contribute to treatment resistance, offering crucial insights into therapeutic failures. Then, state-of-the-art 3D in vitro organ-on-chip (OoC) models are presented that faithfully recapitulate the TME, incorporating patient-derived tumors to enhance clinical relevance. These advanced systems not only overcome the limitations of traditional animal models and 2D cultures but also provide a robust platform for assessing and improving immunotherapeutic regimens. By bridging the gap between bench and bedside, MPS promises to accelerate the development of novel, more effective immunotherapies for solid tumors, potentially transforming cancer treatment in the near future.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 9","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202500098","citationCount":"0","resultStr":"{\"title\":\"Microphysiological Systems in Cancer Research: Advancing Immunotherapy through Tumor Microenvironment-Integrated Organ-On-Chip Models\",\"authors\":\"Fabiana Moresi, Francesco Noto, Jyothsna Vasudevan, Xavier Bisteau, Giulia Adriani, Andrea Pavesi\",\"doi\":\"10.1002/adtp.202500098\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>The intricate tumor microenvironment (TME) poses a significant barrier to effective cancer immunotherapy, requiring innovative strategies to model and address its challenges. Traditional models, such as 2D cultures and animal studies, often fail to capture the TME's dynamic, multicellular, and spatially complex nature, limiting their predictive power for therapeutic outcomes. To overcome these limitations, this review examines innovative microphysiological systems (MPS) that enhance the understanding of tumor-immune interactions and pave the way for more effective immunotherapeutic strategies. First the complex features of the TME and its key players are detailed, elaborating on their dynamic interplay with tumors. Importantly, it is highlighted how these components contribute to treatment resistance, offering crucial insights into therapeutic failures. Then, state-of-the-art 3D in vitro organ-on-chip (OoC) models are presented that faithfully recapitulate the TME, incorporating patient-derived tumors to enhance clinical relevance. These advanced systems not only overcome the limitations of traditional animal models and 2D cultures but also provide a robust platform for assessing and improving immunotherapeutic regimens. By bridging the gap between bench and bedside, MPS promises to accelerate the development of novel, more effective immunotherapies for solid tumors, potentially transforming cancer treatment in the near future.</p>\",\"PeriodicalId\":7284,\"journal\":{\"name\":\"Advanced Therapeutics\",\"volume\":\"8 9\",\"pages\":\"\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-07-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202500098\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advanced Therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://advanced.onlinelibrary.wiley.com/doi/10.1002/adtp.202500098\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://advanced.onlinelibrary.wiley.com/doi/10.1002/adtp.202500098","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Microphysiological Systems in Cancer Research: Advancing Immunotherapy through Tumor Microenvironment-Integrated Organ-On-Chip Models
The intricate tumor microenvironment (TME) poses a significant barrier to effective cancer immunotherapy, requiring innovative strategies to model and address its challenges. Traditional models, such as 2D cultures and animal studies, often fail to capture the TME's dynamic, multicellular, and spatially complex nature, limiting their predictive power for therapeutic outcomes. To overcome these limitations, this review examines innovative microphysiological systems (MPS) that enhance the understanding of tumor-immune interactions and pave the way for more effective immunotherapeutic strategies. First the complex features of the TME and its key players are detailed, elaborating on their dynamic interplay with tumors. Importantly, it is highlighted how these components contribute to treatment resistance, offering crucial insights into therapeutic failures. Then, state-of-the-art 3D in vitro organ-on-chip (OoC) models are presented that faithfully recapitulate the TME, incorporating patient-derived tumors to enhance clinical relevance. These advanced systems not only overcome the limitations of traditional animal models and 2D cultures but also provide a robust platform for assessing and improving immunotherapeutic regimens. By bridging the gap between bench and bedside, MPS promises to accelerate the development of novel, more effective immunotherapies for solid tumors, potentially transforming cancer treatment in the near future.