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通过共培养小鼠胰腺癌类器官和外周血淋巴细胞生成小鼠肿瘤反应性 T 细胞

英文原题:Generation of murine tumour-reactive T cells by co-culturing murine pancreatic cancer organoids and peripheral blood lymphocytes.

查看英文原题

Generation of murine tumour-reactive T cells by co-culturing murine pancreatic cancer organoids and peripheral blood lymphocytes.

PubMed 2022/10/09(内容时间) Biochem Biophys Rep Q3 · IF 3.3(JCR 2025)

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中文摘要

胰腺导管腺癌(PDAC)通常在晚期才被诊断出来,并且会对多种治疗产生耐药性。据报道,癌症免疫疗法在被诊断为上皮性癌的一部分患者中具有显著的临床效果。癌症类器官与自体外周血淋巴细胞共培养提供了一种创新的免疫治疗策略,目前正被越来越多地测试,尽管仍缺乏能够研究个体患者癌症-T细胞相互作用的尖端平台。在本研究中,建立了来自基因工程胰腺癌小鼠模型的胰腺癌类器官培养物,并与自体外周血淋巴细胞共培养,以诱导针对胰腺癌的肿瘤特异性T细胞反应。将自体外周血淋巴细胞与癌症类器官共培养可以成为从小鼠模型外周血中富集肿瘤反应性T细胞的有效策略;这种方法有可能转化应用于人类。外周血淋巴细胞与癌症类器官共培养可以提供一种无偏倚的方法,在个体患者层面评估肿瘤细胞对T细胞介导的致敏作用的敏感性。

展开英文摘要原文

Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at a late stage and becomes resistant to several treatments. Significant clinical effects have been reported for cancer immunotherapies on a subset of patients diagnosed with epithelial cancers. Cancer organoid co-culture with autologous peripheral blood lymphocytes offers an innovative immunotherapeutic approach that is increasingly being tested, although there is a lack of cutting-edge platforms enabling the investigation of cancer-T cell interactions for individual patients.

In this study, a pancreatic cancer organoid culture from a genetically engineered pancreatic cancer murine model was established and co-cultured with autologous peripheral blood lymphocytes to induce a tumour-specific T cell response to pancreatic cancer.

Co-culturing autologous peripheral blood lymphocytes with cancer organoids can be an effective strategy to enrich tumour-reactive T cells from the peripheral blood of murine models; this approach could potentially be transferred to humans. Co-culture of peripheral blood lymphocytes and cancer organoids could provide an unbiased approach to evaluating the sensitivity of tumour cells to T cell-mediated priming on an individual patient level.

论文信息

作者
D'Angelo A、Shibata K、Tokunaga M、Furutani-Seiki M、Bagby S
单位
Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, United Kingdom.United Kingdom
期刊
Biochemistry and biophysics reports2022 Dec
原文标识
PubMed 36237445 · DOI 10.1016/j.bbrep.2022.101365