Semi-supervised analysis of myeloid and T cell behavior in ex vivo ovarian tumor slices reveals changes in cell motility after treatments
Florian Laforêts,
Panoraia Kotantaki,
Beatrice Malacrida,
Samar Elorbany,
Ranjit Manchanda,
Emmanuel Donnadieu,
Frances Balkwill
Affiliations
Florian Laforêts
Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, EC1M6BQ London, UK
Panoraia Kotantaki
Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, EC1M6BQ London, UK
Beatrice Malacrida
Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, EC1M6BQ London, UK
Samar Elorbany
Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, EC1M6BQ London, UK
Ranjit Manchanda
Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, EC1M 6BQ London, UK; Department of Gynaecological Oncology, Barts Health NHS Trust, Royal London Hospital, E1 1BB London, UK; Department of Health Services Research and Policy, London School of Hygiene & Tropical Medicine, WC1H 9SH London, UK
Emmanuel Donnadieu
Université Paris Cité, CNRS, INSERM, Equipe Labellisée Ligue Contre le Cancer, Institut Cochin, 75014 Paris, France
Frances Balkwill
Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, EC1M6BQ London, UK; Corresponding author
Summary: Studies of the high-grade serous ovarian cancer (HGSOC) tumor microenvironment, the most lethal gynecological cancer, aim to enhance the efficiency of established therapies. Cell motility is an important process of anti-tumor response. Using ex vivo human and mouse HGSOC tumor slices combined with time-lapse imaging, we assessed the motility of CD8+ T and myeloid cells. We developed a semi-supervised analysis of cell movements, identifying four cell behaviors: migrating, long migrating, static, and wobbling. Tumor slices were maintained 24h ex vivo, retaining viability and cell movements. Ex vivo treatments with lipopolysaccharide altered CD8+ T and myeloid cell behavior. In vivo chemotherapy reduced ex vivo cell movements in human and mouse tumors and differentially affected CD8+ T and myeloid cells in chemo-sensitive and chemo-resistant mouse models. Ex vivo tumor slices can extend in vivo mouse studies to human, providing a stepping stone to translate mouse cancer studies to clinical trials.
