半监督分析在体外卵巢肿瘤片中髓样和T细胞行为揭示了治疗后细胞运动性的变化。
Semi-supervised analysis of myeloid and T cell behavior in ex vivo ovarian tumor slices reveals changes in cell motility after treatments.
发表日期:2023 Apr 21
作者:
Florian Laforêts, Panoraia Kotantaki, Beatrice Malacrida, Samar Elorbany, Ranjit Manchanda, Emmanuel Donnadieu, Frances Balkwill
来源:
TROPICAL MEDICINE & INTERNATIONAL HEALTH
摘要:
高级别浆膜上皮卵巢癌(HGSOC)肿瘤微环境的研究是为了增强已有治疗的效率,该癌症是最致命的妇科癌症之一。细胞迁移是抗肿瘤反应的重要过程。我们使用人类和小鼠HGSOC肿瘤切片结合时间-lapse成像评估了CD8+ T 和髓样细胞的运动。我们开发了一种半监督的细胞运动分析方法,鉴定出四种细胞行为:迁移、长期迁移、静止和摆动。肿瘤切片能在体外维持24小时,保持细胞活力和运动。体外的脂多糖处理改变了CD8+ T 和髓样细胞的行为。体内的化疗减少了人类和小鼠肿瘤的体外细胞运动,并且在化疗敏感和化疗耐药的小鼠模型中不同地影响了CD8+ T 和髓样细胞。体外肿瘤切片可以扩展体内小鼠研究到人类,为将小鼠癌症研究转化为临床试验提供了一个阶梯。© 2023 The Authors.
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.© 2023 The Authors.