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

doi:10.1016/j.isci.2023.106514

Semi-supervised analysis of myeloid and T cell behavior in ex vivo ovarian tumor slices reveals changes in cell motility after treatments

iScience. 2023 Mar 29;26(4):106514. doi: 10.1016/j.isci.2023.106514. eCollection 2023 Apr 21.

Authors

Florian Laforêts¹, Panoraia Kotantaki¹, Beatrice Malacrida¹, Samar Elorbany¹, Ranjit Manchanda^{2

3

4}, Emmanuel Donnadieu⁵, Frances Balkwill¹

Affiliations

¹ Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, EC1M6BQ London, UK.
² Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, EC1M 6BQ London, UK.
³ Department of Gynaecological Oncology, Barts Health NHS Trust, Royal London Hospital, E1 1BB London, UK.
⁴ Department of Health Services Research and Policy, London School of Hygiene & Tropical Medicine, WC1H 9SH London, UK.
⁵ Université Paris Cité, CNRS, INSERM, Equipe Labellisée Ligue Contre le Cancer, Institut Cochin, 75014 Paris, France.

Abstract

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.

Keywords: Cancer; Immunology; Microenvironment.

Abstract

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