Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses
Tumor-resident immune cells play a crucial role in eliciting anti-tumor immunity and immunomodulatory drug responses, yet these functions have been difficult to study without tractable models of the tumor immune microenvironment (TIME). Patient-derived ex vivo models contain authentic resident immun...
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Taylor & Francis Group
2025-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2466305 |
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| author | Rita Turpin Karita Peltonen Jenna H. Rannikko Ruixian Liu Anita N. Kumari Daniel Nicorici Moon Hee Lee Minna Mutka Panu E. Kovanen Laura Niinikoski Tuomo Meretoja Johanna Mattson Petrus Järvinen Kanerva Lahdensuo Riikka Järvinen Sara Tornberg Tuomas Mirtti Pia Boström Ilkka Koskivuo Anil Thotakura Jeroen Pouwels Maija Hollmén Satu Mustjoki Juha Klefström |
| author_facet | Rita Turpin Karita Peltonen Jenna H. Rannikko Ruixian Liu Anita N. Kumari Daniel Nicorici Moon Hee Lee Minna Mutka Panu E. Kovanen Laura Niinikoski Tuomo Meretoja Johanna Mattson Petrus Järvinen Kanerva Lahdensuo Riikka Järvinen Sara Tornberg Tuomas Mirtti Pia Boström Ilkka Koskivuo Anil Thotakura Jeroen Pouwels Maija Hollmén Satu Mustjoki Juha Klefström |
| author_sort | Rita Turpin |
| collection | DOAJ |
| description | Tumor-resident immune cells play a crucial role in eliciting anti-tumor immunity and immunomodulatory drug responses, yet these functions have been difficult to study without tractable models of the tumor immune microenvironment (TIME). Patient-derived ex vivo models contain authentic resident immune cells and therefore, could provide new mechanistic insights into how the TIME responds to tumor or immune cell-directed therapies. Here, we assessed the reproducibility and robustness of immunomodulatory drug responses across two different ex vivo models of breast cancer TIME and one of renal cell carcinoma. These independently developed TIME models were treated with a panel of clinically relevant immunomodulators, revealing remarkably similar changes in gene expression and cytokine profiles among the three models in response to T cell activation and STING-agonism, while still preserving individual patient-specific response patterns. Moreover, we found two common core signatures of adaptive or innate immune responses present across all three models and both types of cancer, potentially serving as benchmarks for drug-induced immune activation in ex vivo models of the TIME. The robust reproducibility of immunomodulatory drug responses observed across diverse ex vivo models of the TIME underscores the significance of human patient-derived models in elucidating the complexities of anti-tumor immunity and therapeutic interventions. |
| format | Article |
| id | doaj-art-db08a631545c4f98b3e838cbbef2e099 |
| institution | OA Journals |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-db08a631545c4f98b3e838cbbef2e0992025-08-20T02:29:15ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2466305Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responsesRita Turpin0Karita Peltonen1Jenna H. Rannikko2Ruixian Liu3Anita N. Kumari4Daniel Nicorici5Moon Hee Lee6Minna Mutka7Panu E. Kovanen8Laura Niinikoski9Tuomo Meretoja10Johanna Mattson11Petrus Järvinen12Kanerva Lahdensuo13Riikka Järvinen14Sara Tornberg15Tuomas Mirtti16Pia Boström17Ilkka Koskivuo18Anil Thotakura19Jeroen Pouwels20Maija Hollmén21Satu Mustjoki22Juha Klefström23Cancer Cell Circuitry Laboratory, Translational Cancer Medicine, Medical Faculty, University of Helsinki, Helsinki, FinlandHematology Research Unit Helsinki, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, FinlandMediCity Research Laboratory and InFLAMES Flagship, University of Turku, Turku, FinlandCancer Cell Circuitry Laboratory, Translational Cancer Medicine, Medical Faculty, University of Helsinki, Helsinki, FinlandHematology Research Unit Helsinki, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, FinlandCancer Cell Circuitry Laboratory, Translational Cancer Medicine, Medical Faculty, University of Helsinki, Helsinki, FinlandHematology Research Unit Helsinki, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, FinlandDepartment of Pathology, HUSLAB and Haartman Institute, Helsinki University Central Hospital and University of Helsinki, Helsinki, FinlandDepartment of Pathology, HUSLAB and Haartman Institute, Helsinki University Central Hospital and University of Helsinki, Helsinki, FinlandDivision of Breast Surgery, Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, FinlandDivision of Breast Surgery, Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, FinlandComprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, FinlandAbdominal Center, Urology, Helsinki University and Helsinki University Hospital, Helsinki, FinlandAbdominal Center, Urology, Helsinki University and Helsinki University Hospital, Helsinki, FinlandAbdominal Center, Urology, Helsinki University and Helsinki University Hospital, Helsinki, FinlandAbdominal Center, Urology, Helsinki University and Helsinki University Hospital, Helsinki, FinlandDepartment of Pathology, Helsinki University Hospital and Research Program in Systems Oncology, University of Helsinki, Helsinki, FinlandDepartment of Pathology, Turku University Hospital, Turku, FinlandDepartment of Digestive Surgery and Urology, Turku University Hospital and University of Turku, Turku, FinlandImmuno-Oncology, Oncology Research, Orion Corporation, Turku, FinlandCancer Cell Circuitry Laboratory, Translational Cancer Medicine, Medical Faculty, University of Helsinki, Helsinki, FinlandMediCity Research Laboratory and InFLAMES Flagship, University of Turku, Turku, FinlandHematology Research Unit Helsinki, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, FinlandCancer Cell Circuitry Laboratory, Translational Cancer Medicine, Medical Faculty, University of Helsinki, Helsinki, FinlandTumor-resident immune cells play a crucial role in eliciting anti-tumor immunity and immunomodulatory drug responses, yet these functions have been difficult to study without tractable models of the tumor immune microenvironment (TIME). Patient-derived ex vivo models contain authentic resident immune cells and therefore, could provide new mechanistic insights into how the TIME responds to tumor or immune cell-directed therapies. Here, we assessed the reproducibility and robustness of immunomodulatory drug responses across two different ex vivo models of breast cancer TIME and one of renal cell carcinoma. These independently developed TIME models were treated with a panel of clinically relevant immunomodulators, revealing remarkably similar changes in gene expression and cytokine profiles among the three models in response to T cell activation and STING-agonism, while still preserving individual patient-specific response patterns. Moreover, we found two common core signatures of adaptive or innate immune responses present across all three models and both types of cancer, potentially serving as benchmarks for drug-induced immune activation in ex vivo models of the TIME. The robust reproducibility of immunomodulatory drug responses observed across diverse ex vivo models of the TIME underscores the significance of human patient-derived models in elucidating the complexities of anti-tumor immunity and therapeutic interventions.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2466305Breast cancerex vivo modelimmune checkpointIO-treatmentpatient-derived explantsrenal cell carcinoma |
| spellingShingle | Rita Turpin Karita Peltonen Jenna H. Rannikko Ruixian Liu Anita N. Kumari Daniel Nicorici Moon Hee Lee Minna Mutka Panu E. Kovanen Laura Niinikoski Tuomo Meretoja Johanna Mattson Petrus Järvinen Kanerva Lahdensuo Riikka Järvinen Sara Tornberg Tuomas Mirtti Pia Boström Ilkka Koskivuo Anil Thotakura Jeroen Pouwels Maija Hollmén Satu Mustjoki Juha Klefström Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses OncoImmunology Breast cancer ex vivo model immune checkpoint IO-treatment patient-derived explants renal cell carcinoma |
| title | Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses |
| title_full | Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses |
| title_fullStr | Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses |
| title_full_unstemmed | Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses |
| title_short | Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses |
| title_sort | patient derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses |
| topic | Breast cancer ex vivo model immune checkpoint IO-treatment patient-derived explants renal cell carcinoma |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2466305 |
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