Sivakumar Ramya, Chan Marina, Shin Jiye Stella, Nishida-Aoki Nao, Kenerson Heidi L, Elemento Olivier, Beltran Himisha, Yeung Raymond, Gujral Taranjit S
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Department of Surgery, University of Was hington, Seattle, WA, USA.
Oncoimmunology. 2019 Oct 10;8(12):e1670019. doi: 10.1080/2162402X.2019.1670019. eCollection 2019.
Organotypic tumor slices represent a physiologically-relevant culture system for studying the tumor microenvironment. Systematic characterization of the tumor slice culture system will enable its effective application for translational research. Here, using flow cytometry-based immunophenotyping, we performed a comprehensive characterization of the immune cell composition in organotypic tumor slices prepared from four syngeneic mouse tumor models and a human liver tumor. We found that the immune cell compositions of organotypic tumor slices prepared on the same day as the tumor cores were harvested are similar. Differences were primarily observed in the lymphocyte population of a clinical hepatocellular carcinoma case. Viable populations of immune cells persisted in the tumor slices for 7 days. Despite some changes in the immune cell populations, we showed the utility of mouse tumor slices for assessing responses to immune-modulatory agents. Further, we demonstrated the ability to use patient-derived xenograft tumor slices for assessing responses to targeted and cytotoxic drugs. Overall, tumor slices provide a broadly useful platform for studying the tumor microenvironment and evaluating the preclinical efficacy of cancer therapeutics.
器官型肿瘤切片代表了一种用于研究肿瘤微环境的生理相关培养系统。对肿瘤切片培养系统进行系统表征将使其能够有效地应用于转化研究。在此,我们使用基于流式细胞术的免疫表型分析,对由四种同基因小鼠肿瘤模型和一种人类肝脏肿瘤制备的器官型肿瘤切片中的免疫细胞组成进行了全面表征。我们发现,在收获肿瘤核心的同一天制备的器官型肿瘤切片的免疫细胞组成相似。主要在一例临床肝细胞癌病例的淋巴细胞群体中观察到差异。免疫细胞的活细胞群体在肿瘤切片中持续存在7天。尽管免疫细胞群体有一些变化,但我们展示了小鼠肿瘤切片在评估对免疫调节药物反应方面的实用性。此外,我们证明了使用患者来源的异种移植肿瘤切片评估对靶向药物和细胞毒性药物反应的能力。总体而言,肿瘤切片为研究肿瘤微环境和评估癌症治疗药物的临床前疗效提供了一个广泛有用的平台。