The tumor stroma influences immune cell distribution and recruitment in a PDAC-on-a-chip model

by Selleckchem | Jul 20 2023

The dense tumor stroma of pancreatic ductal adenocarcinoma (PDAC) and its secreted immune active molecules provide a barrier for chemotherapy treatment as well as for immune cell infiltration to the tumor core, providing a challenge for immunotherapeutic strategies. Consequently, the investigation of processes underlying the interaction between the tumor stroma, particularly activated pancreatic stellate cells (PSCs), and immune cells may offer new therapeutic approaches for PDAC treatment. In this study, we established a 3D PDAC model cultured under flow, consisting of an endothelial tube, PSCs and PDAC organoids. This was applied to study the role of the tumor microenvironment (TME) on immune cell recruitment and its effect on partly preventing their interaction with pancreatic cancer cells. We observed that stromal cells form a physical barrier, partly shielding the cancer cells from migrating immune cells, as well as a biochemical microenvironment, that seems to attract and influence immune cell distribution. In addition, stromal targeting by Halofuginone led to an increase in immune cell infiltration. We propose that the here developed model setups will support the understanding of the cellular interplay influencing the recruitment and distribution of immune cells, and contribute to the identification of key players in the PDAC immunosuppressive TME as well as support the discovery of new strategies to treat this immune unresponsive tumor.

Comments:

The study you described focuses on investigating the interaction between the tumor stroma, specifically activated pancreatic stellate cells (PSCs), and immune cells in the context of pancreatic ductal adenocarcinoma (PDAC). PDAC is known for its dense tumor stroma, which presents a challenge for both chemotherapy and immune cell infiltration into the tumor core. Understanding the processes underlying this interaction could potentially lead to new therapeutic approaches for PDAC treatment.

To study the role of the tumor microenvironment (TME) on immune cell recruitment and its effect on preventing their interaction with pancreatic cancer cells, the researchers developed a 3D PDAC model cultured under flow. This model consisted of an endothelial tube, PSCs, and PDAC organoids. By utilizing this model, they were able to observe and analyze the behavior and interactions of various cellular components within the TME.

The findings of the study revealed that stromal cells create a physical barrier that partly shields the cancer cells from migrating immune cells. Additionally, the stromal cells contribute to the creation of a biochemical microenvironment that attracts and influences the distribution of immune cells. Targeting the stromal cells using Halofuginone, a compound, resulted in an increase in immune cell infiltration.

The researchers propose that the developed model setups will aid in understanding the cellular interplay that influences the recruitment and distribution of immune cells in PDAC. Moreover, these models can contribute to the identification of key factors and players within the immunosuppressive TME of PDAC. Ultimately, this knowledge can help in the discovery of new strategies to treat this immune-unresponsive tumor.