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用于模拟人胰腺导管腺癌类器官共培养中T细胞亚群变化的体外模型。

In-vitro model to mimic T cell subset change in human PDAC organoid co-culture.

作者信息

Knoblauch M, Ma T, Beirith I, Koch D, Hofmann F, Heinrich K, Aghamaliev U, Sirtl S, Westphalen C B, Nieß H, Reichert M, Angele M K, Regel I, Bazhin A V, Werner J, Ilmer M, Renz Bernhard W

机构信息

Department of General, Visceral, and Transplantation Surgery, LMU Klinikum, Marchioninistr. 15, 81377, Munich, Germany.

German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, Germany.

出版信息

J Cancer Res Clin Oncol. 2023 Nov;149(14):13051-13064. doi: 10.1007/s00432-023-05100-7. Epub 2023 Jul 20.

DOI:10.1007/s00432-023-05100-7
PMID:37470855
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10587248/
Abstract

PURPOSE

Immunotherapies have largely failed as treatment options for pancreatic ductal adenocarcinoma (PDAC). In this field, clinical translational studies into personalized treatment are of fundamental importance. In our study, we model tumor-cell immune-cell interactions in a co-culture of primary human PDAC organoids and matched peripheral blood mononuclear cells (PBMCs).

METHODS

Using flow cytometry, we evaluated changes in T cell subtypes upon co-culture of patient-derived PDAC organoids and matched PBMCs.

RESULTS

After co-culturing PDAC organoids with PBMCs, we observed changes in CD4, CD8 and Treg cell populations. We observed favorable clinical outcome in patients whose PBMCs reacted to the co-culture with organoids.

CONCLUSION

This experimental model allows to investigate interactions between patient derived PDAC organoids and their PBMCs. This co-culture system could serve as a preclinical platform to guide personalized therapeutic strategies in the future.

摘要

目的

免疫疗法在很大程度上未能成为胰腺导管腺癌（PDAC）的治疗选择。在该领域，针对个性化治疗的临床转化研究至关重要。在我们的研究中，我们在原代人PDAC类器官与匹配的外周血单个核细胞（PBMC）的共培养体系中模拟肿瘤细胞与免疫细胞的相互作用。

方法

我们使用流式细胞术评估患者来源的PDAC类器官与匹配的PBMC共培养后T细胞亚群的变化。

结果

将PDAC类器官与PBMC共培养后，我们观察到CD4、CD8和调节性T细胞群体的变化。我们观察到其PBMC对与类器官共培养有反应的患者具有良好的临床结局。

结论

该实验模型能够研究患者来源的PDAC类器官与其PBMC之间的相互作用。这种共培养系统可作为一个临床前平台，在未来指导个性化治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c090/10587248/4c6789b1c201/432_2023_5100_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c090/10587248/5697543c088e/432_2023_5100_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c090/10587248/5f58b8f430c0/432_2023_5100_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c090/10587248/10afc1622f32/432_2023_5100_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c090/10587248/67b368290646/432_2023_5100_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c090/10587248/4c6789b1c201/432_2023_5100_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c090/10587248/5697543c088e/432_2023_5100_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c090/10587248/5f58b8f430c0/432_2023_5100_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c090/10587248/10afc1622f32/432_2023_5100_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c090/10587248/67b368290646/432_2023_5100_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c090/10587248/4c6789b1c201/432_2023_5100_Fig5_HTML.jpg

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