PDAC organoid co-culture model for studying tumor-immune-interactions

Introduction and Purpose Considering the rising morbidity and mortality of pancreatic ductal adenocarcinoma (PDAC), clinical translational studies for early diagnosis, treatment, and prognosis of this tremendous disease are very important. In this study, we studied interactions of tumor and immune cells by establishing a co-culture model of primary human PDAC organoids and peripheral blood mononuclear cells (PBMCs) derived from the same patients, investigating the differentiation of distinct T cell subtypes.

Methods We determined a co-culture method for patient-derived organoids and matched PBMCs to test the differentiation of Memory T cell subtypes and Regulatory T cells (Tregs) by Fluorescence Activated Cell Sorter (FACS).

Results The results were different in 10 patient co-cultures, with three patients showing significant increase of CD4+ Tcm- and Tnaiv-, CD8+ Tcm- and Tnaiv cell population, and decrease of CD4+ Tem- and Teff-, CD8+ Tem- and Teff cell population, compared to those results in PBMCs cultured alone groups. Besides that, the population of Tregs in all PDAC patient co-cultures were higher than that in controls (P value<0.01).

Conclusion Here an autologous co-culture model with patient-derived organoids and PBMCs was established to study the crosstalk between cancerous cells and various immune cells in individual PDAC patients. Having this model available we have a tool at hand to predict the effectiveness of immune therapies thereby helping to improve outcome of our patients.

Publikationsverlauf

Artikel online veröffentlicht:
19. August 2022