Ex Vivo Immuno-Oncology Platform Reveals Spatial T-cell Infiltration Patterns Linked to ATR Inhibition Responses in High-Grade Serous Ovarian Cancer
Year: 2026
Type: article
Abstract: Identifying new therapeutic approaches in high-grade serous ovarian cancer (HGSC) requires the development of more accurate preclinical models that replicate the patient-specific tumor and its microenvironment. To address this, we established immunocompetent patient-derived cultures (iPDC) for HGSC, cultured on a physiologically relevant human omentum gel matrix. We developed a high-throughput platform that combines drug testing, histologic analysis, genomic profiling, single-cell studies, and spatial biomarker discovery. Our results from 47 tumors showed that iPDCs recapitulated the tumor genomic and histologic characteristics while also retaining the intratumoral immune cells. The iPDC treatment responses correlated significantly with the patients' clinical treatment responses. Using iPDCs and single-cell RNA sequencing, we identified potentially effective therapeutic options for patients with recurrent HGSC linked to distinct tumor cell states and mechanisms of resistance. High-throughput drug response profiling with single-cell imaging identified ataxia telangiectasia and Rad3-related inhibitor (ATRi) combined with an immunotherapy targeting autotaxin as a promising new combination treatment for HGSC. Using hyperplexed imaging and spatial analysis, we discovered that ATRi responses were associated with significant increases in both intra- and peritumoral T-cell infiltration, particularly in PD-1+ CD8+ T cells. Additionally, the ATRi-induced reactivation of CD8+ T cells was linked to spatial interactions with replication stress-positive tumor cells. Thus, our iPDC platform presents a representative high-throughput ex vivo model to advance precision oncology in HGSC, uncovering the ATRi-immunotherapy combination as a potentially effective therapeutic option for clinical translation.
Source: Cancer Immunology Research
Authors: Ashwini Sakrepatna Nagaraj, Matilda Salko, Aditi Sirsikar, Ziqi Kang, Erdogan Pekcan Erkan, Elina A. Pietilä, Iga Niemiec, Jie Bao, Giovanni Marchi, Angéla Szabó, María Hincapié-Otero, Anastasia Lundgren, Kirsten Nowlan, Sanna Pikkusaari, Anna Kanerva, Johanna Tapper, Riitta Koivisto-Korander, Heini Lassus, Liisa Kauppi, Sampsa Hautaniemi, Anna Vähärautio, Jing Tang, Eliisa Kekäläinen, Ulla-Maija Haltia, Anni Virtanen, Joonas Jukonen, Tuula Salo, Anniina Färkkilä
Institutions: University of Helsinki, Tampere University, University of Tampere, Helsinki University Hospital, Finnish Cancer Institute, Hospital District of Helsinki and Uusimaa, Oulu University Hospital, University of Oulu, Institute for Molecular Medicine Finland, HiLIFE – Elämäntieteiden Instituutti
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7125119096