A 3D pancreatic tumor model to study T cell infiltration

Abstract

Human T cell infiltration across the endothelium in a 3-dimensional pancreatic tumor model in relation to activation and cellular components.

PDAC-on-chip for in vitro modeling of stromal and pancreatic cancer cell crosstalk

“…49 As demonstrated, 50–55 the stroma represents a histopathological hallmark of pancreatic ductal adenocarcinoma and plays a fundamental role in tumor progression. 56,57 Although recent studies have shown the possibility of modeling the PDAC microenvironment in vitro , 17,20,28,33,34,58–61 the tumor-stroma crosstalk remains extremely challenging to reproduce and monitor in functionally effective models. 62–64…”

“…49 As demonstrated, [50][51][52][53][54][55] the stroma represents a histopathological hallmark of pancreatic ductal adenocarcinoma and plays a fundamental role in tumor progression. 56,57 Although recent studies have shown the possibility of modeling the PDAC microenvironment in vitro, 17,20,28,33,34,[58][59][60][61] the tumor-stroma crosstalk remains extremely challenging to reproduce and monitor in functionally effective models. [62][63][64] We report herein the design, development and characterization of a multilayer PDAC-on-chip device to mimic the tumorstroma relationship through the culture of human pancreatic ductal epithelial cells expressing the activated KRAS and human pancreatic stellate cells, on the same miniaturized platform.…”

“…16 For these reasons, current research is focusing on the development of in vitro PDAC models for a deeper understanding of this pathology, the identification of new biomarkers and the establishment of screening tests, in order to enable the earlier detection of pancreatic cancer and improve the prognosis. [17][18][19][20][21][22] However, one of the major limitations of PDAC in vitro models is the difficulty in replicating the tumor microenvironment surrounding the gland and the PDAC-stroma crosstalk, which constitutes an important feature that significantly affects tumor evolution and drug resistance. [22][23][24][25][26] Among the existing in vitro models, organ-on-achip microfluidic systems represent a powerful tool to reproduce the cancer cell-stroma interactions in a controllable environment and under real-time monitoring.…”

“…30 Recent studies have demonstrated the possibility to include the stromal component on microfluidic platforms to better replicate the PDAC microenvironment by integrating hallmarks of pancreatic cancer desmoplastic tissue. 20,[31][32][33][34] However, the research is still far from a complete understanding of this disease and the mechanisms involved in the PDAC-stroma relationship. Further improvements are therefore needed in the design of microfluidic systems.…”

Activation of STING in the pancreatic tumor microenvironment: A novel therapeutic opportunity

“…Tumor cells interact with endothelial cells, during angiogenesis, primarily to ensure oxygen and nutrient supply to the tumor. However, tumor endothelial cells also shape the overall PDAC tumor microenvironment, notably by acting as a selective barrier that governs immune cells' access to the tumor site [34]. Tumor endothelial cells can therefore regulate the amplitude and the efficacy of anti-tumor responses [7].…”