A1 Refereed original research article in a scientific journal
Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses
Authors: Mutka, Minna; Kovanen, Panu E.; Niinikoski, Laura; Meretoja, Tuomo; Mattson, Johanna; Järvinen, Petrus; Lahdensuo, Kanerva; Järvinen, Riikka; Tornberg, Sara; Mirtti, Tuomas; Boström, Pia; Koskivuo, Ilkka; Thotakura, Anil; Pouwels, Jeroen; Hollmen, Maija; Mustjoki, Satu; Klefstroem, Juha
Publisher: Informa UK Limited
Publishing place: PHILADELPHIA
Publication year: 2025
Journal: OncoImmunology
Journal name in source: OncoImmunology
Journal acronym: ONCOIMMUNOLOGY
Article number: 2466305
Volume: 14
Issue: 1
Number of pages: 12
ISSN: 2162-402X
eISSN: 2162-402X
DOI: https://doi.org/10.1080/2162402X.2025.2466305
Web address : https://doi.org/10.1080/2162402x.2025.2466305
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/491348746
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.
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Funding information in the publication:
The present works were mainly funded through the Business Finland Health program award for project Cancer IO. Klefström research group has received funding from the Academy of Finland, Business Finland, the Finnish Cancer Organizations, Sigrid Juselius foundation, Jane and Aatos Erkko foundation, the Research Council of Finland, and RESCUER project, which has received funding from the European Union’s Horizon 2020 Framework Programme (no. 847912). This work was also supported by the U.S. Department of Defense for Health Affairs through the Breast Cancer Research Program [award no. W81XWH2110773]. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. In addition, funds were received from Sihtasutus Archimedes, Ida Montinin Säätiö, Finnish Cancer Institute, Syöpäjärjestöt, and the iCAN Digital Precision Cancer Medicine Flagship. Mustjoki research group has received funding from Cancer Foundation Finland, Academy of Finland, Sigrid Juselius Foundation, Gyllenberg Foundation, Jane and Aatos Erkko Foundation, State funding for the University-level Health Research in Finland, and HiLIFE fellow funds. Hollmén research group has received funding from Academy of Finland, Cancer Foundations, and the Sigrid Jusélius Foundation.
