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  3. Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses

Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses

  • Oncoimmunology. 2025 Dec;14(1):2466305. doi: 10.1080/2162402X.2025.2466305.
Rita Turpin 1 2,  Karita Peltonen 3 4 5,  Jenna H Rannikko 2,  Ruixian Liu 1,  Anita N Kumari 3 4,  Daniel Nicorici 1,  Moon Hee Lee 3 4,  Minna Mutka 6,  Panu E Kovanen 6,  Laura Niinikoski 7,  Tuomo Meretoja 7,  Johanna Mattson 8,  Petrus Järvinen 9,  Kanerva Lahdensuo 9,  Riikka Järvinen 9,  Sara Tornberg 9,  Tuomas Mirtti 10,  Pia Boström 11,  Ilkka Koskivuo 12,  Anil Thotakura 13,  Jeroen Pouwels 1,  Maija Hollmén 2,  Satu Mustjoki 3 4 5,  Juha Klefström 1 14 15 16
Affiliations

Affiliations

  • 1 Cancer Cell Circuitry Laboratory, Translational Cancer Medicine, Medical Faculty, University of Helsinki, Helsinki, Finland.
  • 2 MediCity Research Laboratory and InFLAMES Flagship, University of Turku, Turku, Finland.
  • 3 Hematology Research Unit Helsinki, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland.
  • 4 Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.
  • 5 iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland.
  • 6 Department of Pathology, HUSLAB and Haartman Institute, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
  • 7 Division of Breast Surgery, Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
  • 8 Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
  • 9 Abdominal Center, Urology, Helsinki University and Helsinki University Hospital, Helsinki, Finland.
  • 10 Department of Pathology, Helsinki University Hospital and Research Program in Systems Oncology, University of Helsinki, Helsinki, Finland.
  • 11 Department of Pathology, Turku University Hospital, Turku, Finland.
  • 12 Department of Digestive Surgery and Urology, Turku University Hospital and University of Turku, Turku, Finland.
  • 13 Immuno-Oncology, Oncology Research, Orion Corporation, Turku, Finland.
  • 14 Finnish Cancer Institute, Helsinki, Finland.
  • 15 FICAN South, Helsinki University Hospital, Helsinki, Finland.
  • 16 Department of Cell & Tissue Biology, University of California, San Francisco, USA.
PMID: 39960413 DOI: 10.1080/2162402X.2025.2466305
Abstract

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.

Keywords

Breast cancer; IO-treatment; ex vivo model; immune checkpoint; patient-derived explants; renal cell carcinoma; tumor immune microenvironment.

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