Tumor organoid-T-cell coculture systems.
Tumor organoid-T-cell coculture systems.
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DOI：
10.1038/s41596-019-0232-9
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发表时间：
2020-01
期刊：
影响因子：
14.8
通讯作者：
Voest EE
中科院分区：
文献类型：
--
作者：
Cattaneo CM;Dijkstra KK;Fanchi LF;Kelderman S;Kaing S;van Rooij N;van den Brink S;Schumacher TN;Voest EE
T细胞是癌症免疫治疗的关键参与者，但在个体患者水平上扩增肿瘤反应性细胞并研究其与肿瘤细胞相互作用的策略是有限的。该方案描述了基于肿瘤类器官和自体外周血淋巴细胞的共培养物的肿瘤反应性T细胞的产生和功能评估。该程序包括两周的初始共培养，其中肿瘤反应性T细胞首先在（IFNγ刺激的）自体肿瘤细胞存在下扩增。随后，可以评价T细胞在识别肿瘤细胞后执行效应子功能（IFNγ分泌、脱粒）的能力，以及它们杀死肿瘤类器官的能力。这种策略的独特之处在于其以抗原不可知的方式使用外周血作为肿瘤反应性T细胞的来源。在两周内，可以获得约33-50%的非小细胞肺癌（NSCLC）和微卫星不稳定（MSI）结直肠癌（CRC）患者样品的肿瘤反应性CD 8 + T细胞群。因此，它允许在个体患者水平上建立用于基于T细胞的免疫疗法的离体测试系统。
T cells are a key player in cancer immunotherapy, but strategies to expand tumor-reactive cells and study their interaction with tumor cells at the level of an individual patient are limited. This protocol describes the generation and functional assessment of tumor-reactive T cells based on co-cultures of tumor organoids and autologous peripheral blood lymphocytes. The procedure consists of an initial co-culture of two weeks in which tumor-reactive T cells are first expanded in the presence of (IFNγ-stimulated) autologous tumor cells. Subsequently, T cells may be evaluated for their capacity to carry out effector functions (IFNγ secretion, degranulation) upon recognition of tumor cells, and their capacity to kill tumor organoids. This strategy is unique in its use of peripheral blood as a source of tumor-reactive T cells in an antigen-agnostic manner. In two weeks, tumor-reactive CD8+ T cell populations can be obtained for ~33-50% of non-small cell lung cancer (NSCLC) and microsatellite instable (MSI) colorectal cancer (CRC) patient samples. It thereby allows the establishment of ex vivo test systems for T cell-based immunotherapy at the level of the individual patient.
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影响因子：
82.9
作者：
Gros A;Parkhurst MR;Tran E;Pasetto A;Robbins PF;Ilyas S;Prickett TD;Gartner JJ;Crystal JS;Roberts IM;Trebska-McGowan K;Wunderlich JR;Yang JC;Rosenberg SA
通讯作者：
Rosenberg SA
影响因子：
3.8
作者：
Tsai S;McOlash L;Palen K;Johnson B;Duris C;Yang Q;Dwinell MB;Hunt B;Evans DB;Gershan J;James MA
通讯作者：
James MA
影响因子：
56.9
作者：
Stronen, Erlend;Toebes, Mireille;Schumacher, Ton N.
通讯作者：
Schumacher, Ton N.
影响因子：
64.8
作者：
Simoni, Yannick;Becht, Etienne;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
64.5
作者：
Neal, James T.;Li, Xingnan;Kuo, Calvin J.
通讯作者：
Kuo, Calvin J.