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Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids.
Cell ( IF 45.5 ) Pub Date : 2018-Sep-06 , DOI: 10.1016/j.cell.2018.07.009 Krijn K Dijkstra 1 , Chiara M Cattaneo 1 , Fleur Weeber 1 , Myriam Chalabi 2 , Joris van de Haar 1 , Lorenzo F Fanchi 1 , Maarten Slagter 1 , Daphne L van der Velden 1 , Sovann Kaing 1 , Sander Kelderman 1 , Nienke van Rooij 1 , Monique E van Leerdam 3 , Annekatrien Depla 4 , Egbert F Smit 5 , Koen J Hartemink 6 , Rosa de Groot 7 , Monika C Wolkers 8 , Norman Sachs 9 , Petur Snaebjornsson 10 , Kim Monkhorst 10 , John Haanen 1 , Hans Clevers 11 , Ton N Schumacher 12 , Emile E Voest 1
Cell ( IF 45.5 ) Pub Date : 2018-Sep-06 , DOI: 10.1016/j.cell.2018.07.009 Krijn K Dijkstra 1 , Chiara M Cattaneo 1 , Fleur Weeber 1 , Myriam Chalabi 2 , Joris van de Haar 1 , Lorenzo F Fanchi 1 , Maarten Slagter 1 , Daphne L van der Velden 1 , Sovann Kaing 1 , Sander Kelderman 1 , Nienke van Rooij 1 , Monique E van Leerdam 3 , Annekatrien Depla 4 , Egbert F Smit 5 , Koen J Hartemink 6 , Rosa de Groot 7 , Monika C Wolkers 8 , Norman Sachs 9 , Petur Snaebjornsson 10 , Kim Monkhorst 10 , John Haanen 1 , Hans Clevers 11 , Ton N Schumacher 12 , Emile E Voest 1
Affiliation
Cancer immunotherapies have shown substantial clinical activity for a subset of patients with epithelial cancers. Still, technological platforms to study cancer T-cell interactions for individual patients and understand determinants of responsiveness are presently lacking. Here, we establish and validate a platform to induce and analyze tumor-specific T cell responses to epithelial cancers in a personalized manner. We demonstrate that co-cultures of autologous tumor organoids and peripheral blood lymphocytes can be used to enrich tumor-reactive T cells from peripheral blood of patients with mismatch repair-deficient colorectal cancer and non-small-cell lung cancer. Furthermore, we demonstrate that these T cells can be used to assess the efficiency of killing of matched tumor organoids. This platform provides an unbiased strategy for the isolation of tumor-reactive T cells and provides a means by which to assess the sensitivity of tumor cells to T cell-mediated attack at the level of the individual patient.
中文翻译:
通过外周血淋巴细胞和肿瘤类器官共培养生成肿瘤反应性 T 细胞。
癌症免疫疗法对一部分上皮癌患者显示出显着的临床活性。尽管如此,目前仍缺乏研究个体患者癌症 T 细胞相互作用和了解反应性决定因素的技术平台。在这里,我们建立并验证了一个平台,以个性化的方式诱导和分析肿瘤特异性 T 细胞对上皮癌的反应。我们证明,自体肿瘤类器官和外周血淋巴细胞的共培养可用于从错配修复缺陷型结直肠癌和非小细胞肺癌患者的外周血中富集肿瘤反应性 T 细胞。此外,我们证明这些 T 细胞可用于评估杀死匹配的肿瘤类器官的效率。该平台为分离肿瘤反应性 T 细胞提供了一种公正的策略,并提供了一种在个体患者水平上评估肿瘤细胞对 T 细胞介导的攻击的敏感性的方法。
更新日期:2018-08-17
中文翻译:
通过外周血淋巴细胞和肿瘤类器官共培养生成肿瘤反应性 T 细胞。
癌症免疫疗法对一部分上皮癌患者显示出显着的临床活性。尽管如此,目前仍缺乏研究个体患者癌症 T 细胞相互作用和了解反应性决定因素的技术平台。在这里,我们建立并验证了一个平台,以个性化的方式诱导和分析肿瘤特异性 T 细胞对上皮癌的反应。我们证明,自体肿瘤类器官和外周血淋巴细胞的共培养可用于从错配修复缺陷型结直肠癌和非小细胞肺癌患者的外周血中富集肿瘤反应性 T 细胞。此外,我们证明这些 T 细胞可用于评估杀死匹配的肿瘤类器官的效率。该平台为分离肿瘤反应性 T 细胞提供了一种公正的策略,并提供了一种在个体患者水平上评估肿瘤细胞对 T 细胞介导的攻击的敏感性的方法。